1915

Allyl isothiocyanate (AITC) occurs abundantly in many cruciferous vegetables such as mustard and horseradish and inhibits cancer cell proliferation through inducing G2/M arrest and apoptosis. Cisplatin is one of the first-line drugs in the treatment of many human cancers in the clinic. In this study, three cancer cell lines, including a highly invasive human ovarian cancer cell line, a colon cancer cell line HCT116 and a breast cancer cell line MCF-7, were used to determine the combinational effects of AITC with cisplatin on cell growth and death. Microscopic morphological changes, survival cell counts and MTT viability assays were employed to analyze cell proliferation and cell viability. Western blot and flow cytometry analysis were used to determine antiapoptotic protein expression and cell cycle distribution after combination treatment with AITC and cisplatin, respectively. Our results show that combination of AITC and cisplatin significantly increases cancer cell death and decreases cell viability in all three human cancer cell lines as compared with each drug alone. Western blot data showed that combination of AITC and cisplatin significantly increased caspase-3 activation and decreased the expression of antiapoptotic protein Bcl-2. More interestingly, combination of AITC and cisplatin appeared to neutralize the increase in the antiapoptotic protein survivin expression induced by single drug treatment. Thus, inhibition of both Bcl-2 and survivin expression in cancer cells by the combination treatment of AITC and cisplatin may at least partially represent the synergy of these two antitumor compounds since both Bcl-2 and survivin are involved in cancer cell survival and drug resistance. In addition, combination of AITC and cisplatin altered cell cycle distribution. Taken together, our data indicate that combination of AITC and cisplatin significantly increases cancer cell death as compared with each drug alone, thus potentially providing a new strategy for cancer treatment.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA