Advanced study of natural sources of anti-cancer

ADVANCED STUDY OF NATURAL SOURCES OF ANTI-CANCER AGENTS

Abstract

Natural products remain an important source of new drugs, new drug leads and new chemical

entities. The plant based drug discovery resulted mainly in the development of anticancer agents

including plants (vincristine, vinblastine, etoposide, paclitaxel, camptothecin, topotecan and

irinotecan), marine organisms (citarabine, aplidine and dolastatin 10) and micro-organisms

(dactinomycin, bleomycin and doxorubicin). Beside this there is numerous agents identified from

fruits and vegetables can used in anticancer therapy. The agents include curcumin (turmeric),

resveratrol (red grapes, peanuts and berries), genistein (soybean), diallyl sulfide (allium), S-allyl

cysteine (allium), allicin (garlic), lycopene (tomato), capsaicin (red chilli), diosgenin

(fenugreek), 6-gingerol (ginger), ellagic acid (pomegranate), ursolic acid (apple, pears, prunes),

silymarin (milk thistle), anethol (anise, camphor, and fennel), catechins (green tea), eugenol

(cloves), indole-3-carbinol (cruciferous vegetables), limonene (citrus fruits), beta carotene

(carrots), and dietary fiber. In this review active principle derived from natural products are

offering a great opportunity to evaluate not only totally new chemical classes of anticancer

agents, but also novel lead compound and potentially relevant mechanisms of action.

(bhanot, (2011) 09-26)

Definition of Cancer

There are many different forms of cancer. Their manifestation is a growth of cells and tissues,

which differ in various aspects from the surrounding tissue. Cancers occur in all living things.

All lifeforms share similar DNA and RNA blueprints and cell physiology. Therefore, the

mechanisms for cancer development and methods for cancer treatment are similar.

(http:/www.digital-recordings.com)

How is Cancer formed?

Cancer cells are formed from normal cells due to a modification / mutation of DNA and/or RNA.

These modifications / mutations can occur spontaneously(II Law of Thermodynamics - increase

of entropy) or they may be induced by other factors such as: nuclear radiation, electromagnetic

1 RGR.SIDDHANTHI COLLEGE OF PHARMACY Tivoli gardens, Patny, Secunderabad.


radiation (microwaves, X-rays, Gamma-rays, Ultraviolet-rays, etc.), viruses, bacteria and fungi,

parasites (due to tissue inflamation/irritation), heat, chemicals in the air, water and food,

mechanical cell-level injury, free radicals, evolution and ageing of DNA and RNA, etc. All these

can produce mutations that may start cancer. Cancer can be called therefore "Entropic Disease"

since it is associated with the increase of entropy of the organism to the point where the

organism cannot correct this itself. External intervention is required to allow the organism to

return to a stable entropic state.


Cancer cells are formed continuously in the organism (it is estimated that there are about 10,000

cancer cells at any given time in a healthy person). The question is why some of these result in

macroscopic-level cancers and some don't. First, not all damaged cells can multiply and many of

them die quickly. Those which have the potential to divide and form cancer are effectively

destroyed by the various mechanisms available to the immune system. This process takes place

continuously. Therefore cancer develops if the immune system is not working properly and/or

the amount of cells produced is too great for the immune system to eliminate. The rate of DNA

and RNA mutations can be too high under some conditions such as: unhealthy environment (due

to radiation, chemicals, etc.), poor diet (unhealthy cell environment), people with genetic

predispositions to mutations and people of advanced age (above 80).


Precursors of Cancer and Cancer Prevention

A weak or non-functioning immune system, poor health, an unhealthy environment and

advanced age (over 80) can contribute to cancer. In the majority of people cancer can be

prevented with proper lifestyle which consists of a low-entropy diet, exercise, sleep, stress

reduction, etc. In most cases cancer develops slowly over many years. With a positive change of

lifestyle and healthy environment this trend can be reversed in the majority of cases (probably in

90% -> 95%) - the cancer will shrink and eventually disappear

(http:/www.digital-recordings.com)2

RGR.SIDDHANTHI COLLEGE OF PHARMACY Tivoli gardens, Patny, Secunderabad.


Mechanisms responsible for Cancer development

Factors which produce cancer cells are: radiation (such as X-rays, nuclear, microwaves, cosmic,

ultrasound, etc.), toxic cell environment, chemicals in the air, water and food, bacteria, viruses

and fungi. Factors which suppress immune functions are the same factors as above plus poor

diet, stress, lack of proper exercise and lack of sufficient rest and sleep.

Traditional Treatment of Cancer

Cancer can be a very scary thing. The survival rates of some cancers is very low and treatments

are not very effective, if one uses traditional medicine (one estimate puts it at 3%). On top of

that, cancer is demonized as this scary thing which is growing in you and is going to kill you.

Many people feel helpless and put blind trust in traditional medicine for treatment. Traditional

medicine is very good in detecting and monitoring cancer but it is very poor and ineffective in

the treatment of cancer. Detection is good and aided by imaging techniques such as NMR, CT-

scan, ultrasound, PET, etc. and many other chemical, genetic, tissue, etc. tests. Below a few

conventional medical treatments techniques are mentioned:

Radiation Therapy

Attempts to locally destroy cancer cells with the various types of radiation such as X-ray,

Gamma-ray, particle beams, isotopes, ultrasound, etc. Beams of radiation are focused

mainly on the cancer growth and doses are calculated to minimize the collateral damage

to surrounding tissues, which nevertheless occurs. This kind of treatment increases the

entropy of the organism, suppresses the immune system, destroys healthy cells and

potentially forms new mutated cells some of which could become cancerous (and

possibly more dangerous than original cancer cells).

Chemotherapy

This aims to destroy the cancer cells with various types of chemicals. The substances

used are supposed to target mainly the cancer cells (sometimes via direct injection to

cancer tissue) and doses are calculated to minimize the collateral damage to surrounding



tissues, which nevertheless occurs. This kind of treatment increases the entropy of the

organism, suppresses the immune system, forms a toxic cell environment, destroys

healthy cells and potentially forms new mutated cells some of which could become

cancerous (and more dangerous than original cancer cells).

Surgery

This is another very invasive technique. Underlying logistics is to locally remove cancer

cells with as few healthy cells as possible. This in turn should stop any further growth,

since there are no cancer cells left in the body. This is a wrong assumption, since it is

very difficult to find the exact boundaries of the cancer growth and remove all cells.

Besides that, cancer cells can enter the blood stream and lymphatic fluid during an

operation and spread to other parts of the body. This kind of treatment also increases the

entropy of the organism, suppresses the immune system and destroys healthy cells and

organs.


All mentioned above methods are very invasive, destroy healthy cells and suppress the immune

system. This approach leads to an increase of entropy of the organism and lowers the chances of

recovery from cancer. All these methods are designed to treat symptoms (cancerous growth), not

the cause of cancer (non-functioning immune system and factors contributing to cancer cells

formation). Since the cause of cancer is not addressed and treatment is not provided, cancer will,

in the majority of cases, spread and recur (the 5-year survival rate for conventional treatments

quoted by The American Cancer Society is 63% and it is much lower for longer periods of time -

one estimate puts it at 3%). Very often cancer patients in hospitals are consuming poor quality

food with hydrogenated fats, which are very unhealthy and dangerous. This only illustrates that a

holistic approach is not considered or followed. Cancer treatment is a very good money-making

machine/system and the patients' welfare is largely ignored.

The described above methods are primitive and barbaric. As a result, millions of people die

prematurely while suffering (according to WHO, the World Health Organization, 7.6 million



people died of cancer in the year 2005). There is also a great effort, burden and expense which is

put on the families and society at large. The only explanation for this state of affairs is total

scientific incompetence, greed and lack of integrity and moral standards on the part of the

majority of cancer researchers and people and organizations who deliver cancer treatments (and

consume billions of dollars in public funding in the process).


What are Anti-Cancer agents?

Anti-cancer agents are the drugs which are used in the treatment of cancer; "anticancer drug";

"an antineoplastic effect"

Plants as source of anti-cancer agents:

The history of plant as source of anti-cancer agents started in earnest in the 1950s with the

discovery and development of the vinca alkaloids (vinblastine and vincristine) and the isolation

of the cytotoxic podophyllotoxins. Vinca alkaloid was responsible for an increase in the cure

rates for Hodgkin’s disease and some forms of leukemia. Vincristine inhibits microtubule

assembly, inducing tubulin self-association into coiled spiral aggregates. Etoposide is a

epipodophyllotoxin, derived from the mandrake plant Podophyllum peltatum andthe wild chervil

Podophyllum emodi. It has also significant activity against small-cell lung carcinoma. Etoposide

is a topoisomerase II inhibitor, stabilizing enzyme–DNA cleavable complexes leading to DNA

breaks. The taxanes paclitaxel and docetaxel has been show antitumor activity against breast,

ovarian and other tumor types in the clinic trial. Paclitaxel stabilizes microtubules and leading to

mitotic arrest. In addition, the camptothecin derivatives irinotecan and topotecan, have shown

significant antitumor activity against colorectal and ovarian cancer respectively. These

compounds were initially obtained from the bark and wood of Nyssacea Camptotheca

accuminata and act by inhibiting topoisomerase I. The taxanes and the camptothecins are

presently approved for human use in various countries (Table 1).

(avidon, 1974)

Table 1: Plant based anticancer agents in clinical practice.



S.No. Compound Uses Status

1. Vincristine Leukemia, lymphoma, Phase

breast, lung, pediatric III/IV

solid cancers and

others

2. Vinblastine Breast, lymphoma, Phase

germ-cell and renal III/IV

cancer

3. Paclitaxel Ovary, breast, lung, Phase

bladder and head and III/IV

neck cancer

4. Docetaxel Breast and lung cancer Phase III

5. Topotecan Ovarian, lung and Phase

pediatric cancer II/III

6. Irinotecan Colorectal and lung Phase

cancer. II/III

Rohitukine the plant alkaloid, isolated from the leaves and stems of Dysoxylum

binectariferum (Maliaceae). Synthetic flavone derived from rohitukine, Flavopiridol

representing the first cyclin-dependent kinase inhibitor to enter the clinical trial. The

mechanism of action involves interfering with the phosphorylation of cyclin-dependent

kinases and arrest cell-cycle progression at growth phase G1 or G2.

(avidon, 1974)

Homoharringtonine an alkaloid isolated from the Chinese tree Cephalotaxus harringtonia

(Cephalotaxacea). The mechanism of action is the inhibition of protein synthesis and blocking

cell-cycle progression. It has shown efficacy against various leukemias. A lung-cancer-specific



antineoplastic agent 4-Ipomeanol is isolated from the sweet potato Ipomoea batata

(Convolvulaceae). The mechanism of action is converted into DNA-binding metabolites upon

metabolic activation by cytochrome P450 enzymes that are present in cells of the lung. DNA

topoisomerase I inhibitor β-lapachone, that induces cell-cycle delay at G1 or S (synthesis) phase

before inducing either apoptotic or necrotic cell death in a variety of human carcinoma cells,

including ovary, colon, lung, prostate and breast.

Beside this there are so many plants which are used in cancer; following enlist the plant which

prevent and target for future studies as potential anticancer agent (Table 2):

Plants used as anti-cancer:

S.No Plant Species Family Plant Part

1. Salvia officinalis Labiatae Leaves

2. Viscum album Loranthaceae Leaves

3. Combretum caffrum Combretaceae Bark

4. Melaleuca alternifolia Myrtaceae Leaves

5. Lavandula angustifolia Labiatae Leaves

6. Aglaia foveolata Meliaceae Fruit

7. Maytenus serrata Celastraceae Seed

8. Tabebuia impetiginosa Bignoniaceae Stem bark and trunk wood

9. Tabebuia rosea Bignoniaceae Stem bark and trunk wood

10. Tabebuia serratifolia Bignoniaceae Stem bark and trunk wood

11. Dipteryx odorata Fabaceae Seed

12. Thapsia garganica Apiaceae Fruit

13. Indigofera tinctoria Leguminosae Aerial part

14. Matricaria chamomilla Asteraceae Flower

15. Erythroxylum pervillei Erythroxylaceae Root

16. Broussonetia papyrifera Urticaceae Entire

17. Cyclopia intermedia Fabaceae Leaves

18. Scutellariae radix, Scutellariae

indica

Labiatae Root

19. Physalis philadelphica Solanaceae Seed7



20. Dysoxylum binectariferum Meliaceae Stem bark

21. Aristotelia chilensis Elaeocarpaceae Leaf and Stem

22. Cyathostemma argentium Annonaceae Root

23. Epimedium hunanense Berberidaceae Aerial parts

24. Croton urucurama Euphorbiacaeae Bark

25. Epilobium hirsutum Onagraceae Entire

26. Pleione bulbocodioides Orchidaceae Tuber

27. Cassia quinquangulata Caesalpiniaceae Root

28. Begonia glabra Begoniaceae Entire

29. Celastrus orbiculatus Celastraceae Entire

30. Croton draco Euphorbiacaeae Aerial parts

31. Smilax sieboldii Liliaceae Entire

32. Ximenia Americana Olacaceae Root

33 Maytenus emarginata Celastraceae Entire

34 Sarcandra glabra Choranthaceae Entire

35 Salvia plebeian Labiatae Aerial

36 Scutellaria barbata Labiatae Entire

37 Ocotea caparrapi Lauraceae Essential oil

38 Caragana cuneata Leguminosae Leaf

39 Croton flavens Euphorbiacaeae Leaf

40 Euphorbia heterophylla Euphorbiacaeae Stem

41 Echites vucatanensis Apocynaceae Latex

42 Thevetia ahouia Apocynaceae Leaf and Stem

43 Thevetia gaumeri Apocynaceae Leaf and Stem

44 Thevetia peruciana Apocynaceae Leaf and Stem

45 Euphorbia ebracteolata Euphorbiacaeae Aerial parts

46 Dioscorea collettii Dioscoreaceae Rhizome

47 Juglans mandshurica Juglandaceae Root



48 Maackia tenuifolia Leguminosae Root

49 Juncus acutus Juncaceae Leaf

50 Hedyotis chrysotricha Rubiaceae Entire

51 Arisaema erubescens Araceae Root

52 Leptadenia hastate Asclepiadaceae Bark

53 Viscum calcaratum Loranthaceae Entire

54 Aphanamixis polystachya Meliaceae Stembark

55 Pratia nummularia Campanulaceae Entire

56 Aeonium arboretum Crassulaceae Leaf

57 Ocotea foetens Lauraceae Branchlets

58 Maytenus canariensis Celastraceae Fruit juice

59 Sedum alboroseum Crassulaceae Entire

60 Euphorbia micractina Euphorbiacaeae Entire

61 Euphorbia prolifera Euphorbiacaeae Latex

62 Scirpus holoschoenus Cyperaceae Inflorescence

63 Dillenia suffruticosa Dilleniaceae Fruit

64 Hypoxis rooperii Hypoxiaceae Tuber

65 Inula linariaefolia Compositae Flowers

66 Ziziphus mauritiana Rhamnaceae Stem bark and Fruit

67 Adiantum macrophyllum Pteridaceae Entire

68 Thalictrum fabri Ranunculaceae Root

69 Scutellaria indica Labiatae Root

70 Hypericum japonicum Guttiferae Entire

71 Cyathea fauriei Cyatheaceae Shoot

72 Fissistigma oldhamii Annonaceae Stem

73 Monnina obtusifolia Polygalaceae Aerial parts

74 Coriolus versicolor Polyporaceae Fruitbody

75 Melastoma malabathricum Melatomataceae Flower

76 Carapa guianensis Meliaceae Seed oil

77 Swietenia humilis Meliaceae Seed

78 Ficus pretoiae Moraceae Sap9



(http:/www.arjournals.org/index.php/ijpm/index)

PLANT DESCRIPTION:

The following chemical compounds were selected for the study, the predicted structures are

obtained from the Pub-Chem. database of National Centre for Biotechnology I information.

(burov, V.V, & korolchenko, 1990)

1. Taxol

Belongs to the family of drugs called mitotic inhibitors. It is obtained via a semi-synthetic

process from Taxusbaccata and other species of Taxus (Yew trees). It is approved for treating

certain cancers like breast cancer, ovarian Cancer and lung cancer.

4. Topotecan (a camptothecin derivative)

Belongs to the family of drugs called topoisomerase inhibitors. It is also called Hycamtin.

Camptothecin, a quinoline-based alkaloid is isolated from Nothapodytesfoetida. It has been

approved for ovarian cancer therapy.

5. Irinotecan

Belongs to a family of drugs called topoisomerase inhibitors. It is a camptothecinanalog and

isolated from Nothapodytesfoetida. Also called CPT 11. It is approved for metastatic colorectal

cancers.

7. Teniposide

Belongs to the family of drugs called mitotic inhibitors.Teniposide is a semisynthetic

podophyllotoxin derived from the root of Podophyllumpeltatum (the May apple or mandrake). It

is used for treating Acute lymphocytic leukemia and neuroblastoma.

Vinca alkaloids:



Vinca minor (common names lesser periwinkle or dwarf periwinkle) is a species offlowering

plant native to central and southern Europe, from Portugal and France north to the Netherlands

and the Baltic States, east to the Caucasus, and also south western Asia in Turkey. Other

vernacular names used in cultivation include small periwinkle, common periwinkle, and

sometimes in the United States, myrtle or creeping myrtle,although this is misleading, as the

name myrtle normally refers to the Myrtus species. (Farnsworth, Draus, R.W., & Bianculli)

Chemical constituents:

Vinca minor contains more than 50 alkaloids, and vincamine is the molecule responsible

for Vinca's nootropic activity.Otheralkaloidsinclude reserpine, reserpinine,akuammicine, majdin

e, vinerine, ervine, vineridine, tombozine, vincamajine, vincanine,vincanidine,vincamone, apovi

ncamine, vincaminol, desoxyvincaminol,[10] vincorine[11] and perivincine. Vinpocetine (brand

names: Cavinton, Intelectol; chemical name: ethyl apovincaminate) is a semisynthetic derivative

alkaloid of vincamine.

Vinblastine

Belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. Vinblastine

alkaloid is extracted from Catharanthusroseus. It is used in the treatment for some types of

cancer including leukaemia, lymphoma, breast and lung cancer.

Chemical structure:


http://en.wikipedia.org/wiki/Vinpocetine

http://en.wikipedia.org/w/index.php?title=Perivincine&action=edit&redlink=1

http://en.wikipedia.org/wiki/Vinca_minor#cite_note-11

http://en.wikipedia.org/w/index.php?title=Vincorine&action=edit&redlink=1

http://en.wikipedia.org/wiki/Vinca_minor#cite_note-10

http://en.wikipedia.org/wiki/Desoxyvincaminol

http://en.wikipedia.org/wiki/Vincaminol

http://en.wikipedia.org/wiki/Apovincamine

http://en.wikipedia.org/wiki/Apovincamine

http://en.wikipedia.org/wiki/Vincamone

http://en.wikipedia.org/w/index.php?title=Vincanidine&action=edit&redlink=1

http://en.wikipedia.org/w/index.php?title=Vincanine&action=edit&redlink=1

http://en.wikipedia.org/wiki/Vincamajine

http://en.wikipedia.org/wiki/Tombozine

http://en.wikipedia.org/wiki/Vineridine

http://en.wikipedia.org/w/index.php?title=Ervine&action=edit&redlink=1

http://en.wikipedia.org/wiki/Nootropic

http://en.wikipedia.org/wiki/Vincamine

http://en.wikipedia.org/wiki/Alkaloids

http://en.wikipedia.org/wiki/Myrtus


Vincristine:

TradeNames: Oncovin ®, Vincasar,Pfs ®

Other Names: Vincristine Sulfate, LCR, VCR

Belongs to the family of plant drugs called vinca alkaloids. Vincristine alkaloid is extracted from

Catharanthus

roseus, belonging to the family Apocynaceae. This species is also known as Vincarosea and has

the alternative

common name of Vinca. Vincristine is an alkaloid derived from flowering periwinkle.

Vincristine is used as a

chemotherapeutic agent for some types of cancers including leukaemia, lymphoma, breast and

lung cancer.


http://chemocare.com/chemotherapy/drug-info/vcr.aspx

http://chemocare.com/chemotherapy/drug-info/lcr.aspx

http://chemocare.com/chemotherapy/drug-info/vincasar-pfs.aspx

http://chemocare.com/chemotherapy/drug-info/oncovin.aspx


Drug Type:

Vincristine is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Vincristine is

classified as a plant alkaloid. For more detail, see "How Vincristine Works" section below.

What Vincristine Is Used For:

Cancers treated with Vincristine include: acute leukemia, Hodgkin's and non- Hodgkin's

lymphoma, neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma, Wilms' tumor, multiple

myeloma, chronic leukemias, thyroid cancer, brain tumors.

It is also used to treat some blood disorders.

Note: If a drug has been approved for one use, physicians sometimes elect to use this same drug

for other problems if they believe it might be helpful.

(chemocare)

How Vincristine Is Given:

Vincristine is given through a vein by intravenous injection (IV push) or infusion (IV). There is

no pill form.

Vincristine is a vesicant. A vesicant is a chemical that causes extensive tissue damage and

blistering if it escapes from the vein. The nurse or doctor who gives Vincristine must be

carefully trained. If you notice pain, redness or swelling at the IV site while you are receiving

Vincristine sulfate, alert your health care professional immediately.

The amount of Vincristine you will receive depends on many factors, including your height and

weight, your general health or other health problems, and the type of cancer you have. Your

doctor will determine your dose and schedule.

Vincristine Side Effects:

Important things to remember about the side effects of Vincristine:

Most people do not experience all of the side effects listed.



Side effects are often predictable in terms of their onset and duration.

Side effects are almost always reversible and will go away after treatment is complete.

There are many options to help minimize or prevent side effects.

There is no relationship between the presence or severity of side effects and the effectiveness of

Vincristine.

The following side effects are common (occurring in greater than 30%) for patients taking

Vincristine:

Hair loss (in 20-70% of patients) may be partial or complete hair loss

Constipation

Low blood counts. Your white and red blood cells and platelets may temporarily decrease. This

can put you at increased risk for infection, anaemia and/or bleeding.

Nadir: Meaning low point, nadir is the point in time between chemotherapy cycles in which you

experience low blood counts.

Onset: 7 days

Nadir: 7-10 days

Recovery: 21 days

Abdominal cramps

Weight loss

Nausea and vomiting

Mouth sores

Diarrhea

Loss of appetite

Taste changes

(chemocare)

Chemical structure:


http://chemocare.com/chemotherapy/what-is-chemotherapy/what-is-nadir.aspx

http://chemocare.com/chemotherapy/side-effects/hair-loss-and-chemotherapy.aspx


Color:

The color name periwinkle is derived from the flower.

EXTRACTION PROCEDURES:

Vincristine and vinblastine:

A sensitive and selective high-performance liquid chromatographic (HPLC) method for the

determination of vinblastine and vincristine in plasma and urine is described. The drugs are

isolated from 1.0 ml of the biological fluid with a solid-phase extraction column (Bond-

ElutDiol®). The HPLC method was combined with electrochemical detection at +850 mV versus

an Ag/AgCl reference electrode. The detection limit is 100 pg for vinblastine and 250 pg for

vincristine with a signal-to-noise ratio of 3, which permits the determination of these compounds

in biological fluids at the nanogram level. Evaluation of the isolation method revealed that the

drug recoveries and the reproducibility of the extraction procedure depend on the batch number

of the solid-phase extraction column used.

Pharmacology:

The vinca alkaloid vincristine induces cytotoxicity by interacting with and disrupting

microtubules, especially those comprising the mitotic spindle apparatus (Rowinsky&Donehower,

1996). Vincristine may bind at low-density high-affinity sites at the ends of the microtubule, with

the effect of inhibiting microtubule assembly, and at low-affinity high-density sites along the

wall of the microtubule, causing disruption of microtubule architecture. For human leukaemia


http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2141.2000.t01-1-02153.x/full#b7

http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2141.2000.t01-1-02153.x/full#b7

http://en.wikipedia.org/wiki/Periwinkle_(color)


cell lines, vincristine causes apoptotic cell death in a manner which relates to the concentration

and time of exposure to the drug (da Silva et al , 1996). For CCRF-CEM and Jurkat cells,

maximum cytotoxicity was found when cells were exposed to 3 µM and 0·1 µM of vincristine for

72 h respectively. However, the cytotoxicity of vincristine is subject to the inoculum effect, in

which an increase in cell density causes a reduction in the intracellular levels and therefore

cytotoxicity of a given dose of the drug (Kobayashi et al , 1992). For Molt-3 cells, maximum cell

kill is associated with 25% saturation of the cellular vincristine binding sites, and the lesser effect

of the drug at high cell density could be explained by the lack of drug molecules to saturate

cellular binding sites sufficiently (Kobayashi et al , 1998). In most experimental models,

resistance to vincristine is associated with decreased drug accumulation and retention, a

phenomenon which is usually associated with the cellular expression of P-glycoprotein and the

MDR phenotype (Rowinsky&Donehower, 1996).

Single-agent studies of vincristine in the therapy of childhood ALL were performed in the 1960s,

mainly in children with disease which had relapsed after therapy with methotrexate and 6-

mercaptopurine. With doses of 0·06 mg/kg/week (Heyn et al , 1966) or 2 mg/m2/week

(Karon et al , 1966), complete remission (CR) rates of 50–60% were obtained, although the study

of Karon et al (1966) suggested that vincristine had no advantage over a placebo in remission

maintenance. However, monthly pulses of vincristine, in association with prednisolone, have

been shown to improve the disease-free survival of children with ALL (Bleyer et al ,

1991; Childhood ALL Collaborative Group, 1996).

In modern protocols for the therapy of childhood ALL, vincristine forms one of the mainstays of

remission induction therapy. In most protocols, vincristine is administered during remission

induction as a weekly intravenous bolus at a dose of 1·5 mg/m2 (Chessells et al ,

1995; Evans et al , 1998) or 2·0 mg/m2 (Veerman et al , 1996), and the maximum dose is

conventionally capped at 2–2·5 mg in view of the risk of toxicity (Rowinsky&Donehower,

1996). Vincristine also plays a role in the intensification/consolidation therapy (Chessells et al ,

1995; Nachman et al , 1998) and maintenance therapy (Chessells et al , 1995; Veerman et al ,

1996) of ALL in many protocols.

The clinical pharmacology of vincristine has been investigated for children with ALL. After

bolus intravenous administration, the pharmacokinetics of vincristine are characterized by large

inter- and intrapatient variations in parameters such as clearance, volume of distribution and 16



elimination half-life (Gidding et al , 1999). Peak plasma concentrations of 100–400 nM are only

briefly achieved after an intravenous bolus of vincristine; the t1/2α (initial or elimination half-life)

of approximately 8 min reflecting the rapid cellular uptake and extensive tissue binding of the

drug. Indeed, in the majority of children, plasma levels fall to below 5 nm by 60 min (de

Graaf et al , 1995), and the long t1/2β (half-life of the terminal phase of elimination) of

approximately 14 h means that plasma levels of 1–2 nM are maintained for relatively long

periods of time. Although the clearance values for children are generally greater than those for

infants and adults (Gidding et al , 1999), it is not certain whether vincristine clearance decreases

with age during childhood (Crom et al , 1994; Gidding et al , 1999). In addition, there is no clear

relationship between vincristine neurotoxicity and systemic exposure (Crom et al , 1994). When

administered as a continuous infusion of 0·5 mg/m2/24 h for 5 d after a 1·5-mg/m2 intravenous

loading dose, mean steady-state plasma vincristine concentrations of 1·7 nM are maintained with

acceptable toxicity (Pinkerton et al , 1988). Although the cerebrospinal fluid (CSF) penetration of

vincristine has not been determined in children, adult studies have shown vincristine levels in the

CSF to be 20- to 30-fold lower than concurrent plasma concentrations (Rowinsky&Donehower,

1996).

Vincristine is rapidly taken up by cells, and the ratio of intracellular to extracellular

concentrations ranges from 150- to 500-fold for various human haemopoietic cell lines

(Rowinsky&Donehower, 1996). For mice bearing human rhabdomyosarcomaxenografts,

sensitivity to vincristine was associated with prolonged retention of the drug after a single

intraperitoneal injection (Horton et al , 1988). The only studies of vincristine in relation to

leukaemic blasts from children with ALL have related to in vitro drug sensitivity testing by

means of the MTT assay (Klumper et al , 1995), in which a mean IC50of 0·71 µM (range < 0·05 to

> 50) was demonstrated.

In summary, although vincristine has an established role in the therapy of ALL, little is known of

the relationship between the clinical and cellular pharmacology of the drug in vivo for childhood

ALL. In vitro studies have highlighted the importance of the degree of saturation of vincristine

binding sites and time of exposure for vincristine cytotoxicity in human leukaemia cell lines.

Therefore, studies are needed to determine the relationship between systemic exposure to

vincristine, as determined by pharmacokinetic measurements, and intracellular levels, binding

site saturation and retention in leukaemic blasts. In this respect, a loading dose of vincristine 17



followed by a prolonged infusion (Pinkerton et al , 1988) may optimize therapy with this agent,

especially in the initial stages of remission induction therapy when a high leukaemic burden

could potentially generate a positive inoculum effect (Kobayashi et al , 1998).

SCREENING METHOD:

It has been claimed that the micronucleus test (MNT) is a simple and practical in vivo

cytogenetic screening method for mutagens. To evaluate the MNT as an initial screening

method, mice and Chinese hamsters were treated in vivo with triethylene melamine (0.016,

0.032, 0.062, 0.125, or 0.25 mg/kg), azathioprine (50, 200, or 500 mg/kg), colchicine (0.625,

1.25, or 2.5 mg/kg) or caffeine (100, 200, or 250 mg/kg). The treated animals were examined by

means of the MNT, chromosome analysis (CA) and sister chromatid exchange (SCE) scoring.

For the MNT and CA, each dose level was applied twice to 3–4 animals with an interval of 24 h.

For the SCE test, the animals received a treatment with 5-bromodeoxyuridine (BUDR) and 5-

fluorodeoxyuridine (FUDR), during which time the test compounds were administered once.

Triethylene melamine was clearly positive in all three tests, whereas azathioprine was positive in

the MNT and CA, but negative in the SCE. Colchicine was positive in the MNT, but negative in

the other two tests. Caffeine gave negative results in all three tests. The results indicate that the

MNT can detect not only chromosome-breaking agents but also spindle poisons. This is a great

advantage over other cytogenetic methods as far as screening is concerned, as is the technical

simplicity with which the test can be performed. Furthermore, the basic treatment for the in vivo

SCE method using BUDR and FUDR was shown to be positive in the MNT and CA.

A review of the literature dealing with the MNT in which the results of testing 150 agents are

reported confirms the present findings, i.e., the usefulness of the MNT for screening clastogens

and spindle poisons.

We conclude that, among the various in vivo cytogenetic methods using mammalian somatic

cells, the MNT is the most practical when applied as an initial screening test in laboratories in

which a large number of compounds are to be tested



Etoposide :

Belongs to the families of drugs called podophyllotoxin derivatives and topoisomerase inhibitors.

Etoposide is a semisynthetic derivative of the podophyllotoxins, an epipodophyllotoxin. It is

used in treating various types of cancers including bladder cancer, brain tumours, cervical

cancer, ependyoma, germ cell tumor and gestationaltrophoblasticneoplasia.

Trade names: Toposar®, VePesid®, Etopophos®

Other name: VP-16, Etoposide phosphate

EXTRACION PROCEDURE:

Etoposide was extracted from 100 µL aliquots of plasma treated with deuteratedetoposide as the

internal standard using an ether based liquid-liquid extraction (LLE). Following evaporation and

reconstitution of the organic supernatant, HPLC separation was achieved on an Agilent Zorbax

SB-C18 Chemocare.com uses generic names in all descriptions of drugs. VP-16 is the trade

name for etoposide. VePesid and etopophos and toposar or etoposide phosphate are other names

for etoposide. In some cases, health care professionals may use the trade name VP-16 or other

names VePesid or etopophos or toposar or etoposide phosphate when referring to the generic

drug name etoposide.

(O'Dwyer PJ, 1985)

Drug type: Etoposide is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug.

This medication is classified as a "plant alkaloid" and "topoisomerase II inhibitor." (For more

detail, see "How this drug works" section below).

What this drug is used for:

Testicular, bladder, prostate, lung, stomach, and uterine, cancers. Hodgkin's and non-Hodgkin's

lymphoma, mycosis fungoides, Kaposi's sarcoma, Wilm's tumor, rhabdomyosarcoma, Ewing's

sarcoma, neuroblastoma, brain tumors.

It also may be given as high-dose therapy in bone marrow transplant setting.



Note: If a drug has been approved for one use, physicians may elect to use this same drug for

other problems if they believe it may be helpful.

How this drug is given?

In tablet form by mouth.

As an infusion into the vein (intravenous, IV), as a short infusion or as a continuous infusion

over 24 hours.

Etoposide is considered an irritant. An irritant is a chemical that can cause inflammation of the

vein through which it is given. If the medication escapes from the vein it can cause tissue

damage. The nurse or doctor who gives this medication must be carefully trained. If you

experience pain or notice redness or swelling at the IV site while you are receiving etoposide,

alert your health care professional immediately.

The amount of etoposide that you will receive and the method it is given depends on many

factors, including your height and weight, your general health or other health problems, and the

type of cancer or condition being treated. Your doctor will determine your dose, schedule and

how it will be given.

(chemocare, http://chemocare.com/chemotherapy/drug-info/etoposide.aspx#.ukK3-dKBk5E)

chemical structure:



Pharmacology:

Etoposide is a potent cytostatic. It seems to be more effective when administered in multiple than

as a single dose. Its mode of action differs from that of mitosis inhibitors such as colchicine and

the vinca alkaloids. It produces a therapeutic synergism with a number of drugs and this

promises a considerable broadening of the range of indications for etoposide

SCREENING METHOD:

BMY-40481-30 is a new, water-soluble derivative and probable prodrug of etoposide

characterized by the presence of a phosphate group in position 4′ of the E ring of the etoposide

molecule. The compound was only weakly cytotoxic in vitro and, consequently, an investigation

of its antitumor activity was conducted in several murine and human tumor (xenograft) models.

Etoposide was administered ip or po whereas BMY-40481-30 was given ip, po or iv. The

potency of the derivative, when administered parenterally, as defined on the basis of maximum

tolerated dose (MTD), was less than the parent compound on a weight (mg/kg) basis in some

experiments but comparable to etoposide in other instances. Comparison at the MTD of the two

compounds showed that BMY-40481-30 administered ip was as active as etoposide against ip

P388 leukemia. BMY-40481-30 given iv was more active than etoposide given ip in two of five

experiments versus iv P388 leukemia, but the two compounds were comparably active in the

other three studies. Of particular interest was the finding that the derivative was more active than

the parent compound at many of the comparable (on a mg/kg basis) dose levels of both evaluated

po versus iv P388 leukemia; MTD levels were not achieved, and hence not compared, for either

compound using the po route of administration. Both etoposide and BMY-40481-30 yielded



comparable maximum effects against ic P388 leukemia, ic L1210 leukemia, and sc B16

melanoma, but etoposide was more efficacious versus sc M5076 sarcoma. In addition to murine

tumors, the HCT-116 human colon carcinoma was tested in a subrenal capsule model in athymic

(nude) mice; both compounds demonstrated similar tumor inhibitory effects. Lastly, the human

lung carcinomas, LX-1 and H2981, implanted sc into nude mice, showed either equivalent

sensitivity to etoposide and BMY-40481-30, or a slightly enhanced sensitivity to the parent

compound, in several experiments performed. BMY-40481-30 is a novel derivative and probable

prodrug of etoposide with excellent solubility in water and antitumor activity generally

comparable to that of the parent compound as demonstrated in several preclinical models.

CHEMICAL STRUCTURE OF ANTICANCER DRUGS

Taxol:

Biological activity is the result of chemical compound's interaction with biological entity. In

clinical study biological entity is represented by human organism. In preclinical testing it is the

experimental animals (in vivo) and experimental models (in vitro). Biological activity depends

on peculiarities of compound (structure and physico-chemical properties), biological entity

(species, sex, age, etc.), mode of treatment (dose, route, etc.). Any biologically active compound

reveals wide spectrum of different effects. Some of them are useful in treatment of definite

diseases but the others cause various side and toxic effects. Total complex of activities caused by

the compound in biological entities is called the "biological activity spectrum of the

substance".Biological activity spectrum of a compound presents every its activity despite of the

difference in essential conditions of its experimental determination. Then the results are



validated and predicted., In case when the probabilities for more than 400 different activities are

estimated simultaneously, and the ideal training set should include all referenced biologically

active compounds from literature, the best estimate of prediction's quality can be calculated by

leave one out cross validation. Each of the compounds is subsequently removed from the training

set and the prediction of its activity spectrum is carried out on the basis of the remaining part of

the training set. The result is compared to the known activity of a compound, and the maximal

error of prediction (MEP) is calculated through the all compounds and activities. Etaposide and

Irinotecan are DNA intercalators. Now a bandwith of drugs for the cancer treatment is

analysed,it must be improved and lot of studies have to be continued to ensure its activity invitro

and invivo. (50 x 2.1mm, 5 micron) column. A mobile phase gradient operating at a flow of 300

µL/min increased from 25 to 90 %B over 2 minutes where mobile phase A was 10 mM

ammonium acetate (aq) acidified with 0.1% formic acid and mobile phase B was

acetonitrile:methanol:formic acid (50:50:0.1, v:v:v). An LLOQ of 1.00 ng/mL was achieved

using multiple reaction monitoring of the etoposide-ammonium adduct ion on an AB Sciex API

4000™ operating in positive ESI.

Paclitaxel:

An isocratic high-performance liquid chromatographic method has been developed and validated

for the quantitative determination of paclitaxel (Taxol®), a novel antimitotic, anticancer agent, in

human plasma. The analysis required 0.5 ml of plasma, and was accomplished by detection of

the UV absorbance of paclitaxel at 227 nm following extraction and concentration. The method

involved extraction of paclitaxel from plasma, buffered with 0.5 ml of 0.2 M ammonium acetate

(pH 5.0), onto 1-ml cyano Bond Elut columns. The eluent was evaporated under nitrogen and

low heat, and reconstituted with the mobile phase, acetonitrile-methanol-water (4:1:5, v/v/v)

containing 0.01 M ammonium acetate (pH 5.0). The samples were chromatographed on a

reversed-phase octyl 5 μm column. The retention time of paclitaxel was 10 min. The validated

quantitation range of the method was 10–1000 ng/ml (0.012–1.17 μM) of paclitaxel in plasma.

Standard curve correlation coefficients of 0.995 or greater were obtained during validation

experiments and analysis of clinical study samples. The observed recovery for paclitaxel was

83%. Epitaxol, a biologically active stereoisomer, and baccatin III, a degradation product, were

also chromatographically separated from taxol by this assay. The method was applied to samples 23



from a clinical study of paclitaxel in cancer patients, providing a pharmacokinetic profiling of

paclitaxel.

Combinations of the herbal drugs to be given to anti-cancer patient:

(1) Drugs and Herbs of Ayurveda used according to specific system location

(a) Brain Cancer - Ayurvedic Herbs

–Mandukaparni (Bacopa monerea)

-Kastoori Bhairav Rasa with combination of divya herbs.

(b) Oropharyngeal Cancers - Ayurveda Herbs

– Kasamarda (cassia oxidentalis)

-Mahalaxmi vilas Rasa

(c) Lung Cancers - Ayurveda Herbs

- Pippali (Piper longum)

-Hirak Rasayan

(d) Stomach Cancers - Ayurveda Herbs

– Shatavari (Asparagus resimosus)

-Amlaki (Philanthus amblica)

-Banga Bhasma

-Aloe-Vera

-Amaltas (Casia fistula)

-Bhoy-Amli (Philanthus nurare)

-Sarphunkha (Tephrosia purpura)

(e) Intestinal Cancers - Ayurveda Herbs

-Shigru (Moringa olifera)

-Panchamrut purpti



(f) Female Genital Cancers - Ayurvedic Herbs

-Ashoka (Seraka Ashoka)

-Vaikranta Bhasma

(g) Mail Genital Cancers - Ayurveda herbs

-Triphala (Three myrobelans)

-Makardhvaja

(h) Liver Cancers - Ayurveda Herbs

-Bhumvamalaki

-Arogyavardhini

(i) Blood Cancer - Ayurveda Herbs

-Anantmula (Hermidesmus indicus)

-Suvarna Vasant Malti Rasa

(j) Bone Cancers - Ayurveda Herbs

-Aabha Gugglu

-Madhu Malini Vasant Rasa

(k) Breast Cancers - Ayurvedic Herbs

-Gojivha

-Chinchabhallataka

(l) Skin Cancers - Ayurveda Herbs

-Manjishtha (Rubia cordifolia)

-Samira Panaga Rasa

-Kaishore Gugglu

-Gandhak Rasayan

(2) Drugs of Ayurveda According to the general condition of the patient



-Sutashekhar rasa

-Punarnava Mandura

-Aarogya Vardhini

-Avipattikar Churna

-Kamadhugdha Rasa

-Swarna Gairika

-Laghu Vasant Malti

-Hirak Bhasma

(3) Drugs pf Ayurveda according to the Agni of the patient

-Drakshasava

-Swarna Makshika Bhasma

-Shivakshara Pachan Churna

-Chitrakadi Vati

-Trifala Churna

-Panchskhar Churna

(4) Drugs of Ayurveda used in all cancers

-Kanchnara Gugglu

-Kaishore Gugglu

-Bhallatak Phalmajja Churna

-Trifala Gugglu

-Tribang Bhasma

-Shilajatu Vati

-Aabha Gugglu

-Laksha Gugglu

(5) Drugs of Ayurveda according to Nadi



-Vishtinduka for Vatta Nadi

-Katuki for Pitta Nadi

-Bhallatak for Kapha Nadi

-Combination of above for dvidosha Nadi

-All three for Tridosh Nadi

(6) Decoctions of Ayurveda for purification of body cells

Prescribed to all patients. One, two or more from the following

-Varunadi Kwath

-Panchvalkal Kwath

-Manjishthadi Kwath

-Dashmula Kwath

-Varunadi Kwath

-Kanchnar Kwath

(7) Drugs of Ayurveda for symptomatic relief

-All Gugglu preparations for pain relief, and tumor reducing.

-Gandhak Rasayan for infections

-Bilva, Mayurpichha, Tankan, sphatika for loose motions and vomiting

-Shigru, Chitrakadi vati for pain in the abdomen

-Rohitaka, Shamaka yoga for pain in pancreas and renal colic.

-Shirashooladi vajra rasa, for headaches

-Beejapuraka and trikatu in jaundice

-Vasa+Goat milk in bleeding

-Aabha+Madhumandura in bone pain

(8) DARF methodology to reduce the side effects of chemotherapy



Some of the most common side effects of chemotherapy

-Mucositis- in the form of mouth ulcers, vomiting, loose motions etc.

-Phlebitis-In the form of skin discolouration with veins paining

-Leukopenia-In the form of low w.b.c. counts with increased chances of infection.

-Hair loss

Therapies three days prior to chemotherapy-

-Sadhya Snehan-One teaspoon cow ghee+one teaspoon salt, mixed and consumed at morning,

empty stomach with hot water.

-Manjishthadi Kwath and Kanchnar Gugglu. During chemotherapy, coriander leaves juice frshly

prepared about 20 to 30 gms, twice a day.

Treatment during Radiotherapy

-Sadhya snehan + Matra basti for three days

-A piece of tamarind to be kept in mouth during R.T. is advised in mouth and throat cancers.

-A vaginal tampon of Erand oil is applied daily in vaginal cervical and rectal cancers.

-A mrudu virechan –Mild laxative is always advised during R.T, except in vaginal and cervical

cancers.

-Symptomatic treatment as per the situation is offered.

(ayurveda-cancer.org)

Present regimens:

Why Are Our Anticancer Herbal Remedies Potent?

The herbal remedies used at HCC are produced using high-techniques rather than traditional

methods. We identified, analyzed and refined 16 new anticancer herbal remedies from >200 sorts

of anticancer herbs.

The active ingredients of our anticancer herbal remedies are extracted and concentrated using

pharmaceutical industry processes of investigating western medicine.



To qualify and quantify the products the effective dose of anticancer herbal remedies has been

examined at levels of microgram /ml by cancer killing tests in vitro, animal tumor models in

vivo, and cancer patients in clinical studies at university hospitals.

The anticancer herbal remedies are manufactured in GMP workshops and they are made in

capsule forms. This is convenient to oral administration by patients.

All anticancer herbal remedies meet with the US-FDA regulations and they are effective, safe,

and only have slight side effects.

There is no conflict in the treatment results between western medicine and herbal remedies. Both

anticancer western medicine and anticancer herbal remedies can be used at the same time to

attain synergetic effects.

Clinical studies of CT scan and MRI imaging have shown regression and shrinking of cancer

lesions in patients who received the standard anticancer herbal therapy at HCC.

Why Are Anticancer Herbal Treatments Effective?

Doctors at HCC are experienced herbal specialists. They have studied, trained and practiced

western medicine and herbal medicine at Tongji Medical University in China, Hanover Medical

School in Germany, and Harvard Medical School in the USA. By applying the principle of cell

cycle in light of design of cancer treatment, they have developed 5 herbal treatment regimens,

which exerts 1+1>3 therapeutic result. Therefore, their clients are more effectively treated

compared to traditional and conventional herbal therapeutics.



Cocktail Herbal Therapy is to use the triple-anticancer herbal remedies plus a cocktail

anticancer herbal extract liquid for treatment of conditions of cancer. Patients take 2 to 3

different hi-tech anticancer herbal capsules plus a cocktail herbal extract liquid at the same time

to combat a cancer condition. One of the herbal remedies blocks mitosis of cancer cells in phase

M, and 2 others attack cancer cells in phases G1, S and G2 by destroying the membranes of

cancer cells, damaging mitochondria in the cytoplasm and microtubules in cytoskeleton, and

splitting DNA in the nucleus. The cocktail herbal extract liquid is an anticancer enhancer that

uplifts the therapeutic effect. Each of the anticancer herbal components in this regimen hits a key

point of cancer cell cycle. The cocktail herbal therapy is usually used as an intensive cancer

therapy for patients with critical cancer conditions.

Intensive Herbal Therapy is administered in the case of critical cancer conditions that are life-

threatening and require emergency treatment. The purpose of this treatment is to quickly control

the growth of primary tumor and metastatic lesions. Patients from out of Massachusetts are

admitted to HCC for a week to receive a high-dose of intensive herbal therapy which consists of

3 to 4 different anticancer herbal remedies. Generally, patients take about 15 capsules per

medication, every 6 hours. The dose is dependent upon patient’s body weight and physical

condition. 30



Maintenance Herbal Therapy is indicated for patients who have finished the intensive

anticancer herbal therapy and whose cancer conditions are stable. The goal of this treatment is to

attain a healing, complete remission, partial remission or extension of life-span. Generally, this

treatment is done at home. Patients in Massachusetts should visit HCC weekly or biweekly.

Patients from out of Massachusetts should visit HCC monthly or bimonthly, and patients from

out of the USA should visit HCC every 2 to 3 months to evaluate the treatment effect.

Targeting Herbal Therapy is to use our specific anticancer herbal remedies to target tumors in

certain organs or tissues, such as the LDL-110 herbal remedy targets human breast cancer, liver

cancer, lung cancer and prostate cancer. It also has high concentration in lymphatic tissue that

targets lymphoma and metastases in lymph nodes. Anticancer-2 selectively accumulates in large

bowel that targets colorectal carcinoma. Carcinoma of the esophagus and stomach is sensitive to

ingredient rabdosia. Anticancer-1 and Anticancer-3 can pass the brain blood barrier (BBB) to

target brain tumors and metastases in bony tissue.

Combination Herbal Therapy: The anticancer herbal therapies can be used as the first-chosen

treatment of conditions of cancer patients. They can also be used in combination with western

medicine and radiotherapy for synergetic results. Cancer patients who have failed to

chemotherapy or other treatments can still use the hi-tech herbal therapy, which provide a

possible chance of healing, complete remission, partial remission or extension of life-span. HCC

cooperates with patients’ primary care physicians and oncologists to provide top quality service

to clients and protect patients from clinical complications and sideeffects.

Side Effects of the hi-tech anticancer herbal remedies are mild, including multiple bowel

movements and slight decrease in white blood cell count in approximately 7% of individuals

who have had previous medical histories of dysfunction of the digestive system and hemapoietic

system.

Expected Results: Generally, as demonstrated by CT scan and MRI imaging, patients suffering

from malignant tumor or cancer, who have received standard anticancer herbal therapy at HCC,

may see a stable cancer condition by 2 months, approximately 20-30% regression of primary

tumor and metastatic lesions by 3 months; 30-40% regression of primary tumor and metastatic 31



lesions by 6 months; 40-60% regression of primary tumor and metastatic lesions by 9 to 12

months; and further regression of primary tumor and metastatic lesions by continuation

treatments. Then, a maintenance anticancer therapy is required to protect the patient from

recurrence of cancer condition.

One should understand that each patient’s genetics is different from another, each patient’s

physical condition is different from another, each patient’s cancer condition is also different from

others, and various cancer types have different responses to herbal therapy. Therefore, some of

the cancer patients may be healed, and some of them may reach complete remission, while others

may obtain partial remission or even no response to the herbal therapy at all.

Candidate.Physical.Conditions:

* Patients should be positive and confident in fighting against cancer with the hi-tech anticancer

herbal therapies. Patients who have enrolled in the herbal therapy program should not give up or

discontinue their treatment.

* Patients should have good general health, normal meals, no major dysfunction of the heart,

lung, liver and kidney, and be able to walk.

* Normal appetite and meals are important because the hi-tech anticancer herbal remedies are

made in capsule forms that are administered by mouth.

* The expected patient’s life-span in pretreatment should be longer than 3 months because we

usually see remarkable regression of cancer lesion(s) by 2 to 3 months after starting treatment.

* Bring past medical records, pathology diagnosis, recent CT scan and/or MRI image disks (also

written reports) when patient visits HCC. These data are available from your primary care

physicians and oncologists.

(hmcboston.com)



DISCUSSION:

Planning experiments and choosing the activities on which the compound has to be tested, one

should have in mind the necessity of balancing between the novelty of pharmacological action

and the risk to obtain negative result in experimental testing. Certainly, one will also take into

account the particular interest in some kinds of activity, experimental facilities, etc.

The accuracy of prediction is about 90%.

CONCLUSION:



All the drugs estimated show a good tendency to fight against the neoplastic cancer, also the

drug Irinotecan is against Alzimers disease. Teniposide is not as worthy as others as it is a

cardiotoxic and It is suggested that health care professionals and consumers should be aware of

the potential for adverse interactions with these herbs, question their patients on their use of

them, especially among patients whose disease is not responding to treatments as expected, and

urge patients to avoid herbs that could confound their cancer care.

BIBLIOGRAPHY:

al., b. e. ((2011) 09-26). international journal of phytomedicine 3 .

avidon. (1974). chim-pharm.j.(Rus).

ayurveda-cancer.org. http://www.ayurveda-cancer.org/cancerdrugs.htm.

bhanot. ((2011) 09-26). international journal of phytomedicine .

burov, V.V, & korolchenko. (1990). bull. natl. center for biological active compounds(Rus).



chemocare. (n.d.).

http://chemocare.com/chemotherapy/drug-info/vincristine.aspx#.ukK3VdKBk5F .

chemocare. http://chemocare.com/chemotherapy/drug-info/etoposide.aspx#.ukK3-dKBk5E.

Farnsworth, N., Draus, F., R.W., & Bianculli, J. (n.d.). "studies on vinca major L. (Apocynaceae)

I. Isolation of perivicine". Journal of the American pharmaceutical Association 49

(9):589.doi:10.1002/jps.3030490908 .

hmcboston.com. http://www.hmcboston.com/HCC/.

http:/www.arjournals.org/index.php/ijpm/index. (n.d.).

http:/www.digital-recordings.com. http:/www.digital-recordings.com/publ/cancer.html.

O'Dwyer PJ, L.-j. B. (1985). current status of an active anticancer drug. New England J Med

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