Activation of the mitochondria-driven pathway of apoptosis in human PC-3 prostate cancer cells by a novel hydrophilic paclitaxel derivative, 7-xylosyl-10-deacetylpaclitaxel.

摘要: Paclitaxel, a natural product originally isolated from Taxus brevifolia, belongs to the most successful anticancer drugs. Nevertheless, its poor water solubility represents considerable disadvantage in clinical use, and novel derivatives with improved pharmacological features are required. We 7-xylosyl-10-deacetylpaclitaxel chinensis, which reveals higher than paclitaxel. This compound induced mitotic cell cycle arrest apoptosis as measured by flow cytometry, DNA laddering, transmission electron microscopy. Pro-apoptotic Bax Bad protein expression was up-regulated anti-apoptotic Bcl-2 Bcl-XL down-regulated, lead disturbance of mitochondrial membrane permeability activation caspase-9. In turn, caspase-9 activated downstream caspases-3 -6, but not caspase-8. Bid also caspase-3. Reversely, treatment caspase-10-specific inhibitor could protect PC-3 cells 7-xylosyl-10-deacetyl-paclitaxel-triggered apoptosis. Moreover, had no effect on CD95 NF-kappaB proteins, indicating that through mitochondrial-dependent pathway cells.