Curcumin Enhances Chemosensitivity and Apoptosis in T24 Bladder Cancer Cells through Inhibition of the Ras/ MAPK Signaling Pathway: submitted: Feb 3, 2018 Accepted: Mar 10, 2018 Published online: Mar 15, 2018

Background. Curcumin (CUR), a natural phenolic compound, has been recently reported to exert antitumor actions in variety of cancers; however, the exact mechanism(s) is not clear. In this study we investigated whether CUR could inhibit Ras/MAPK pathway and enhance mitomycin C (MMC) cytotoxicity in T24 bladder cancer cells. Methods. T24 cells were cultured with different concentrations of CUR (5, 10, 20 μM) alone or combined with 10 μg/ml MMC. At the end of 72 h culture, cell viability was assessed by MTT assay; apoptosis by flow cytometry; total Ras and ERK1/2 by immunohistochemistry and western blotting. Results. In comparison to cells exposed to MMC alone, cells treated with combined MMC and either 10 or 20 μM CUR showed reduced cell proliferation, disrupted morphological appearance, and increased subG0/G1 apoptotic events. This inhibition was associated with marked reduction of Ras and ERK1/2 expression. Likewise, cells treated with 10 or 20 μM CUR alone showed significant inhibition, while the effect of 5 μM was less obvious. Conclusion. Resistance of T24 cells to cytotoxic effect of MMC is dependent, at least partially, on Ras/ERK activation. CUR at concentrations of 10 and 20 μM in combination with low dose MMC induced toxic synergism in T24 cells. Clinical translation of this experimental study may be reasonable in light of wide safety margin and availability of CUR