Guggulsterone Induces Apoptosis and Inhibits Lysosomal-Dependent Migration in Human Bladder Cancer Cells

The survival rate and therapeutic options of bladder cancer patients have improved little in recent decades. Guggulsterone (GS), a phytoestrogen, has been investigated as an anticancer drug in various malignancies. The present study aimed to evaluate the anticancer effect of E-isomer and Z-isomer GS in the human bladder cancer cell lines TSGH8301 (low-grade) and T24 (high-grade) and its underlying mechanisms. E-isomer GS reduced the survival rate in both low- and high-grade human bladder cancer cells. Colony formation was inhibited after GS treatment. Moreover, cell cycle arrest accompanied by reduced cyclin A, increased p21 and caspase-dependent apoptosis was observed upon GS treatment. Moreover, GS treatment downregulated p-mTOR, mTOR, p-Akt and LC3expression in bladder cancer cells. In addition, GS reduced migration ability with a decrease in integrin-focal adhesion kinase (FAK) and myosin light chain (MLC). The GS-mediated migration suppression was prevented by the lysosomal inhibitor NH4Cl in human bladder cancer cells. Current findings suggest that GS treatment may serve as a potential anticancer therapy for both low- and high-grade urothelial carcinoma.