This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, C.-C. Articles by Wu, Y.-C. Search for Related Content PubMed PubMed Citation Articles by Wu, C.-C. Articles by Wu, Y.-C.

Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan

Requests for reprints: Chin-Chung Wu or Yang-Chang Wu, Graduate Institute of Natural Products, Kaohsiung Medical University, 100 Shin-Chuan 1st Road, Kaohsiung, Taiwan. Phone: 886-7-312-1101, ext. 2197; Fax: 886-7-311-4773. E-mail (C-C. Wu): ccwu{at}kmu.edu.tw

Pristimerin, a naturally occurring triterpenoid, has been shown to cause cytotoxicity in several cancer cell lines. However, the mechanism for the cytotoxic effect of pristimerin was never explored. In the present study, human breast cancer MDA-MB-231 cells treated with pristimerin (1 and 3 µmol/L) showed rapid induction of apoptosis, as indicated by caspase activation, DNA fragmentation, and morphologic changes. Pretreatment of a pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-fmk) completely prevented pristimerin-induced apoptosis. Treatment of tumor cells with pristimerin resulted in a rapid release of cytochrome c from mitochondria, which preceded caspase activation and the decrease of mitochondrial membrane potential. In addition, neither benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone nor permeability transition pore inhibitor cyclosporin A markedly prevented pristimerin-induced mitochondrial cytochrome c release. Pristimerin did not significantly alter the protein level of Bcl-2 family members (Bcl-2, Bcl-X_L, and Bax), nor did it induce Bax translocation. Moreover, Bcl-2 overexpression fails to prevent pristimerin-induced apoptosis. The generation of reactive oxygen species in MDA-MB-231 cells was also not affected by pristimerin. In a cell-free system, pristimerin induced cytochrome c release from isolated mitochondria. Taken together, these results suggested that pristimerin is a novel mitochondria-targeted compound and may be further evaluated as a chemotherapeutic agent for human cancer.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 1/21/05; revised 5/27/05; accepted 6/14/05.

This article has been cited by other articles:

				W.-Y. Chen, F.-R. Chang, Z.-Y. Huang, J.-H. Chen, Y.-C. Wu, and C.-C. Wu Tubocapsenolide A, a Novel Withanolide, Inhibits Proliferation and Induces Apoptosis in MDA-MB-231 Cells by Thiol Oxidation of Heat Shock Proteins J. Biol. Chem., June 20, 2008; 283(25): 17184 - 17193. [Abstract] [Full Text] [PDF]