Isoliquiritigenin Induces Apoptosis through Caspases and Reactive Oxygen Species Signaling Pathways in Human Bladder Cancer Cells

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.