Original article Crude extract of Rheum palmatum inhibits migration and invasion of U-2 OS human osteosarcoma cells by suppression of matrix metalloproteinase-2 and -9 Shu-Chun Hsu a , Ju-Hwa Lin a , Shu-Wen Weng b,c , Fu-Shin Chueh d , Chien-Chih Yu e , Kung-Wen Lu f, ** ,i , W. Gibson Wood g , Jing-Gung Chung a,h, * ,i a Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan b Graduate Institute of Chinese Medicine, China Medical University, Taichung 404, Taiwan c Department of Chinese Medicine, Taichung Hospital, Department of Health, Executive Yuan, Taichung 403, Taiwan d Department of Health and Nutrition Biotechnology, Asia University, Taichung 413, Taiwan e School of Pharmacy, China Medical University, Taichung 404, Taiwan f School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 404, Taiwan g Department of Pharmacology, School of Medicine, Geriatric Research, Education and Clinical Center, VA Medical Center, University of Minnesota, Minneapolis, MN 55455, USA h Department of Biotechnology, Asia University, Taichung 413, Taiwan article info Article history: Received 28 March 2013 Accepted 25 April 2013 Available online 1 June 2013 Keywords: crude extract of Rheum palmatum U-2 OS human osteosarcoma cells migration invasion abstract Osteosarcoma is the most common primary bone malignancy and primarily occurs in adolescents and young adults. Crude extract of Rheum palmatum L. (CERP) has been used as a traditional Chinese medicine for different diseases and there is experimental evidence that it may have anti-cancer effects. However, there is no information showing that CERP can affect the mobility of human osteosarcoma cells. In this study we determined the effects of CERP on U-2 OS human osteosarcoma cells. We found that CERP significantly inhibited the migration and invasion of U-2 OS cells. CERP also reduced the activity of matrix metalloproteinase (MMP)-2 and MMP-9 and decreased expression levels of the proteins FAK, GRP78, PKC, HIF-1, SOS1, VEGF, PI3K, GRB2, Ras, p-ERK1/2, ERK1/2, p-p38, JNK1/2, p-JNK1/2, MEKK3, MKK7, PERK, p-PERK, iNOS, COX-2, NF-kB p65, IRE-1, UPA, and RhoA in U-2 OS cells. Confocal laser microscopy revealed that CERP decreased the expression of NF-kB p65, RhoA and Rock 1. These in vitro studies suggest that CERP may * Corresponding author. Department of Biological Science and Technology, China Medical University, No 91, Hsueh-Shih Road, Taichung 40402, Taiwan. ** Corresponding author. School of Post-Baccalaureate Chinese Medicine, China Medical University, No 91, Hsueh-Shih Road, Taichung 40402, Taiwan. E-mail addresses: [email protected](K.-W. Lu), [email protected](J.-G. Chung). i These authors contributed equally to this work. Available online at www.sciencedirect.com journal homepage: http://www.e-biomedicine.com BioMedicine 3 (2013) 120 e129 2211-8020/$ e see front matter Copyright ª 2013, China Medical University. Published by Elsevier Taiwan LLC. All rights reserved. http://dx.doi.org/10.1016/j.biomed.2013.04.008
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Crude extract of Rheum palmatum inhibitsmigration and invasion of U-2 OS humanosteosarcoma cells by suppression of matrixmetalloproteinase-2 and -9
Shu-Chun Hsu a, Ju-Hwa Lin a, Shu-Wen Weng b,c, Fu-Shin Chueh d,Chien-Chih Yu e, Kung-Wen Lu f,**,i, W. Gibson Wood g,Jing-Gung Chung a,h,*,i
aDepartment of Biological Science and Technology, China Medical University, Taichung 404, TaiwanbGraduate Institute of Chinese Medicine, China Medical University, Taichung 404, TaiwancDepartment of Chinese Medicine, Taichung Hospital, Department of Health, Executive Yuan, Taichung 403, TaiwandDepartment of Health and Nutrition Biotechnology, Asia University, Taichung 413, TaiwaneSchool of Pharmacy, China Medical University, Taichung 404, Taiwanf School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 404, TaiwangDepartment of Pharmacology, School of Medicine, Geriatric Research, Education and Clinical Center,
VA Medical Center, University of Minnesota, Minneapolis, MN 55455, USAhDepartment of Biotechnology, Asia University, Taichung 413, Taiwan
a r t i c l e i n f o
Article history:
Received 28 March 2013
Accepted 25 April 2013
Available online 1 June 2013
Keywords:
crude extract of Rheum palmatum
U-2 OS human osteosarcoma cells
migration
invasion
* Corresponding author. Department of Biolo40402, Taiwan.** Corresponding author. School of Post-Bacca40402, Taiwan.
E-mail addresses: [email protected] These authors contributed equally to thi
2211-8020/$ e see front matter Copyright ªhttp://dx.doi.org/10.1016/j.biomed.2013.04.00
a b s t r a c t
Osteosarcoma is the most common primary bone malignancy and primarily occurs in
adolescents and young adults. Crude extract of Rheum palmatum L. (CERP) has been used as
a traditional Chinese medicine for different diseases and there is experimental evidence
that it may have anti-cancer effects. However, there is no information showing that CERP
can affect the mobility of human osteosarcoma cells. In this study we determined the
effects of CERP on U-2 OS human osteosarcoma cells. We found that CERP significantly
inhibited the migration and invasion of U-2 OS cells. CERP also reduced the activity of
matrix metalloproteinase (MMP)-2 and MMP-9 and decreased expression levels of the
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