Abstract
4731
Breast cancer is the second leading cause of cancer deaths in women in the US. Current treatment options include chemotherapy, radiotherapy and surgery. Naturally occurring plant compounds have shown pharmacological and therapeutic activities against different types of tumors. Perillyl alcohol (POH) is a naturally occurring monoterpene found in fruits and vegetables. Cis-jasmone (CJ) and methyl jasmonate (MJ) belong to the family of plant stress hormones currently being studied as novel anticancer agents. We investigated the cytotoxic and apoptosis-inducing activities of these three plant compounds on two breast cancer cell lines (MDA-MB-231 and MDA-MB-435) using proliferation and cytotoxicity assays, DNA content analyses, fluorescence microscopy and western blotting techniques. The concentration of each compound that inhibited the proliferation of MB-231 and MB-435 cells by 50% (IC50) were 2.0,1.2mM (POH); 1.7, 0.8mM (CJ); and 1.5, 1.3mM (MJ) respectively. POH caused cell cycle arrest in the G0/G1 phase in both cell lines. CJ and MJ caused a block in the G0/G1 phase in MB-435 and in the S phase in MB-231 cells. Hoechst staining confirmed the induction of apoptosis after 24hr treatment. Compared to their respective controls, each of the three plant compounds caused a 4-fold increase in apoptosis in MB-231 cells. In MB-435 cells, POH and CJ caused 2-fold increases and MJ a 14-fold increase in apoptosis. Western blotting and flow cytometric data showed an increase in the release of cytochrome-c into the cytosol, a decrease in procaspase-3 level and a corresponding increase in caspase-3 activity. We concluded that the release of cytochrome c following exposure to these plant compounds led to the formation of the apoptosome complex and the consequent activation of caspase-3, the executioner of apoptosis. Both the monoterpene (POH) and the jasmonates (CJ and MJ) have potential as possible anticancer agents and require further investigation.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]
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