Androgen-Responsive Lncap and Androgen-Independent Du145 Prostate Cancer Cells Display Different Taxol Sensitivities

Abstract Taxol has been used as anti-cancer compound against prostate, ovarian, and metastatic breast cancer. While the most obvious effect of taxol is bundeling of microtubules and mitotic arrest, recent studies have demonstrated that taxol is able to induce intranucleosomal DNA fragmentation and typical morphological features of apoptosis in a number of solid tumor cells. These results indicate that taxol may exert its anti-tumor effects via secondary mechanisms which may or may not be related to its primary effects on microtubules. It has been shown that taxol-induced microtubular changes and G2/M arrest are associated with the release of the electron transfer protein cytochrome C from mitochondria into the cytosol. Cytochrome C then binds to APAF-1 (a human homolog of the ced-4 gene of C. elegans), which binds, cleaves, and activates caspase- 9, ultimately resulting in the cleavage and activity of caspase-3. We investigated the effects of taxol (100nM) on microtubules, on DNA, and on the pre-apoptotic mitochondrial events using LNCaP and DU145 prostate cancer cells.