Objective: Arsenic trioxide (ATO) is a potent antitumor agent used to treat acute promyelocytic leukemia, and recently solid tumors including bladder cancers. However, a mechanism to explain its antitumor activity in bladder cancers is unclear. Here, we investigated the role of protein kinase C (PKC) in ATO-induced apoptosis and inhibition of proliferation in bladder cancer cells. Methods: T24 human bladder carcinoma cells were incubated with different concentrations of ATO in the presence or absence of PMA (PKC activator) or H7 (PKC inhibitor). Cell proliferation was assessed by MTT assay, and apoptosis by TUNEL and electron microscopy. Flow cytometry was used to analyze cell cycle distribution, radioimmunoassay to measure PKC activity, and Western blot analysis to detect caspase-3. Results: ATO inhibited proliferation and induced apoptosis of T24 cells in a dose-dependent manner, caused an increase of percentage of cells in the G1 phase and a decrease in the S and G2 phases, and upregulated the expression of activated caspase-3 and reduced PKC activity. These effects were abrogated by PMA, but enhanced by H7. Conclusions: PKC is involved in the anticancer activity of ATO for T24 bladder cancer cells, suggesting that targeting the PKC pathway may represent a potential approach to enhance the efficacy of ATO to treat bladder cancers.

Keywords:
Arsenic trioxide, Protein kinase C, Bladder cancer, Proliferation, Apoptosis
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© 2009 S. Karger AG, Basel
2009
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