Background: Bladder cancer is the second most common genitourinary malignancy and the eleventh most common cancer worldwide. Dihydroartemisinin (DHA), a first-line antimalarial drug, has been found to have potent antitumor activity. In our previous study, a novel dihydroartemisinin derivative Mito-DHA5 synthesized in our laboratory has a stronger anti-tumor activity than DHA. In this study, we investigated the apoptotic effect of Mito-DHA5 on bladder cancer T24 cells and molecular mechanisms underlying.
Methods: Antitumor activity in vitro was evaluated by MTT and cloning formation assays. Mitochondrial membrane potential (MMP) was detected by JC-1 probe and ROS levels were measured by specific kit. The expression of caspase-3, Bcl-2 and Bax in T24 cells was evaluated by Western blotting.
Results: The results showed that Mito-DHA5 reduced cell viability with an IC50 value of 3.2 μM in a dose-dependent manner, induced T24 cell apoptosis at both early and late stages, increased the production of ROS and decreased MMP. Mito-DHA5 could down-regulate the expression of Bcl-2 and Caspase-3, and up-regulate the expression of Bax and cleaved Caspase-3.
Conclusion: These data suggested that Mito-DHA5 had a potent inhibitory effect on T24 bladder cancer cell growth and induced these cells apoptosis associated with mitochondrial pathway.