Epicatechin Stimulates Mitochondrial Activity and Selectively Sensitizes Cancer Cells to Radiation Hosam A. Elbaz, Ph.D. November 07 th , 2013 Department of Radiation Oncology, Center for Molecular Medicine and Genetics, Wayne State University Detroit, MI 48201.
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Epicatechin Stimulates Mitochondrial Activity and Selectively Sensitizes Cancer
Cells to Radiation
Hosam A. Elbaz, Ph.D.
November 07th, 2013Department of Radiation Oncology,
Center for Molecular Medicine and Genetics, Wayne State University
Detroit, MI 48201.
Overview
• Introduction
• What is (-)-Epicatechin?
• Experimental methods
• (-)-Epicatechin and Mitochondrial Respiration
• (-)-Epicatechin and Radiosensitization
• Potential Mechanisms
• Conclusion and Future Directions
Introduction
• Radiotherapy is ideal for most solid tumors.
• Radiation resistance and adverse effects are frequently encountered.
• Most cancer types exhibit 40-60% reduction in mitochondrial activity and rely on aerobic glycolysis for energy (Warburg effect).
• Radiosensitizing agents would improve therapeutic outcome.
What is (-)-Epicatechin?
• A natural polyphenolic flavanol– Flavonoid family– Natural ingredient in cacao, green tea and dark chocolate– Antioxidant properties
• Molecular Weight: 290.268097 Da • IUPAC name: (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-chromene-3,5,7-triol• It has a number of beneficial health effects.
(-)-Epicatechin stimulated mitochondrial respiration and ETC protein expression
Hüttemann H et al. FASEB J. 2012; vol. 26 no. 4 1413-1422
Short term treatment of 40 µM (-)-Epicatechin enhances cytochrome c oxidase activity
p < 0.05;
* and ** compared to control
0 5 10 15 20 25 30 350
20
40
60
80
100
120
140
160 Control 5 min
20 min
Cytc [µM]
CcO
Spe
cific
Acti
vity
[O
2 nm
ol/m
in/m
g of
tota
l pro
tein
]
**
*
General hypothesis(-)-Epicatechin
↑ COX activity↑ Mitochondrial respiration in cancer cells
↓ The Warburg metabolism and ↑ ROS production
in cancer cells
↑ Cellular stress
↑ Sensitivity to cell death
Experimental methods• Cytochrome c oxidase activity
• Cell lines:• Panc-1• MIA PaCa-2• U87• Normal human dermal fibroblasts (NHDF)
• Clonogenic survival assay
• Enzymes for checkpoint and OXPHOS complexes• P-Chk2: phosphorylated checkpoint kinase protein 2 at Thr68• p21. • P-Erk2: phosphorylated extracellular kinase 2• OXPHOS complexes-