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Research Paper
Anti-Proliferative effect of ursolic acid on multidrug resistant hepatoma cells R-HepG2 by apoptosis induction
Dong-Mei Zhang, Patrick Ming-Kuen Tang, Judy Yuet-Wa Chan, Hung-Ming Lam, Shannon Wing-Ngor Au, Siu-Kai Kong, Stephen Kwok-Wing Tsui, Mary Mui-Yee Waye, Thomas Chung-Wai Mak and Kwok-Pui Fung
Volume 6, Issue 9September 2007
Pages 1381 - 1389
DOI: 10.4161/cbt.6.9.4528
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Many studies have demonstrated that ursolic acid (UA) could potently inhibit the proliferation of a wide variety of cancer cells; however, its anti-tumor effect on multidrug resistant carcinoma was rarely reported. In the present study, UA exhibited cytotoxicity on the multidrug resistant human hepatoma cell line R-HepG2 with the IC50 value of 20 μM at 48 h. Our findings indicated that UA was not a binding substrate for P-glycoprotein and could not modulate the expression and activity of P-glycoprotein. This provides a possible mechanism on UA circumvention of the drug resistance. Mechanistic study demonstrated that UA induced apoptosis on R-HepG2 cells via both extrinsic and intrinsic apoptotic pathways, including the activation of caspase cascade and the release of cytochrome c and AIF from mitochondria to cytosol. Furthermore, in vivo study showed a significant inhibition on the growth of R-HepG2 cells in the UA-treated group (15 mg/kg/day, i.v.), with negligible damage towards the heart and the liver. The present study suggests the potential of UA as chemotherapeutic agent and provides further insight into the molecular basis of UA-induced apoptosis on multidrug resistance human hepatoma cells.
Authors
- Dong-Mei Zhang
- The Chinese University of Hong Kong, Hong Kong, China
- Patrick Ming-Kuen Tang
- The Chinese University of Hong Kong, Hong Kong, China
- Judy Yuet-Wa Chan
- The Chinese University of Hong Kong, Hong Kong, China
- Hung-Ming Lam
- The Chinese University of Hong Kong, Hong Kong, China
- Shannon Wing-Ngor Au
- The Chinese University of Hong Kong, Hong Kong, China
- Siu-Kai Kong
- The Chinese University of Hong Kong, Hong Kong, China
- Stephen Kwok-Wing Tsui
- The Chinese University of Hong Kong, Hong Kong, China
- Mary Mui-Yee Waye
- The Chinese University of Hong Kong, Hong Kong, China
- Thomas Chung-Wai Mak
- The Chinese University of Hong Kong, Hong Kong, China
- Kwok-Pui Fung
- The Chinese University of Hong Kong, Hong Kong, China
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF
If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.
