Pristimerin induces caspase-dependent apoptosis in MDA-MB-231 cells via direct effects on mitochondria.

Content Provider	Semantic Scholar
Author	Wu, Chin-Chung Chan, Michel Chen, Wen-Ying Tsai, Ching-Yi Daphne Wu, Yang-Chang
Copyright Year	2005
Abstract	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 micromol/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.
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://mct.aacrjournals.org/content/molcanther/4/8/1277.full.pdf
PubMed reference number	16093444v1
Volume Number	4
Issue Number	8
Journal	Molecular cancer therapeutics
Language	English
Access Restriction	Open
Subject Keyword	3,4-Methylenedioxyamphetamine Alanine Aminolevulinic Acid Antineoplastic Agents Apoptosis BCL2 gene Caspase Activation Caspase Inhibitors Cultured Cell Line Cyclosporine DNA Fragmentation Ketones Mammary Neoplasms Membrane Potentials Micromole Mitochondrial Diseases Reactive Oxygen Species Valine benzyloxycarbonyl-Phe-Ala-fluormethylketone cancer cell pristimerin
Content Type	Text
Resource Type	Article