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  • Title: Novel dihydroartemisinin derivative Mito-DHA5 induces apoptosis associated with mitochondrial pathway in bladder cancer cells.
    Author: Xiao L, Xu C, Lin P, Mu L, Yang X.
    Journal: BMC Pharmacol Toxicol; 2022 Jan 20; 23(1):10. PubMed ID: 35057867.
    Abstract:
    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, wound healing 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, cleaved-caspase3, mitochondrial Cyt-C, Bcl-2, Bax and PARP 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 and induced T24 cell apoptosis in a dose-dependent manner, increased the production of ROS and decreased MMP. Mito-DHA5 could down-regulate the expression of Bcl-2, mitochondrial Cyt-C, Caspase-3, PARP and up-regulate the expression of Bax and cleaved Caspase-3. CONCLUSIONS: 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.
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