Arsenic trioxide-mediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines

We studied the effect of arsenic trioxide (As2O3) on prostate and ovarian c arcinoma cell lines. As2O3 has been shown to be effective in leukemia, and acute promyelocytic leukemia in particular, both ill vitro and ill vivo. As model cell lines, we used DU145 and PC-3 for prostate cancer and MDAH 2774 for ovarian cancer. New modalities of treatment are essential in these kin ds of cancers, which produce a high death toll. The 3-(4,5-dimethyl-thiazoy l-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to evaluate cytotox icity. Flow cytometric analysis and mono-oligo nucleosome detection-based E LISA were used to determine the apoptosis. Isobologram analysis was used to evaluate synergism and/or the additive effects of As2O3 and conventional c hemothtrapeutic agents, We clearly demonstrated that As2O3 has significant cytotoxic effect on both prostate and ovarian carcinoma cell lines. The dos e range of As2O3 in all three cell lines was similar to 10(-6) at. The mech anism underlying cytotoxicity of As2O3 was shown to be apoptosis, The exper iments by butylated hydroxyanisole showed that the cytotoxic effect of As2O 3 was not through superoxide generation, There was no synergism, but the ad ditive effects of As2O3 were demonstrated with cisplatin, adriamycin, and e toposide. We strongly suggest that As2O3 alone or in combination with conve ntional chemotherapeutic agents be evaluated further as a new agent for the treatment of prostate and ovarian cancers.