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Isoliquiritigenin induces apoptosis through caspases and reactive oxygen species signaling pathways in human bladder cancer cells

Background: Isoliquiritigenin (ISL) is a flavonoid isolated from the roots of various species of licorice plants. Objectives: Mechanisms underlying ISL-induced cell death were investigated in 5637 human bladder cancer cell line. Materials and Methods: Cell viabilities were measured with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide and cell counting kit-8 assay. Cell cycle analysis, caspase activity assay, western blotting, and reactive oxygen species (ROS) assay were also used to investigate the anticancer effects of ISL on 5637 cells. Results: ISL (100–500 μg/ml) inhibited cancer cell proliferation and increased sub-G1 cell cycle phase ratios. ISL-induced cell death resulted in reduced Bcl-2 and increased Bax. ISL also activated caspase-3 and -9 and increased the levels of intracellular ROS generated. In addition, TG100-115 (transient receptor potential [TRP] melastatin 7 inhibitor) and tranilast (TRP vanilloid 2 inhibitor) each exerted a synergistic effect with ISL on ISL-induced apoptosis. Conclusion: These findings suggest that ISL causes apoptosis in 5637 cancer cell line. Therefore, ISL may be a potential anticancer drug for treating bladder cancer and a good anticancer supplement.