ABSTRACT
OBJECTIVE: Bladder cancer is one of the most prevalent genitourinary malignancies. Despite active chemotherapy regimens, patients with bladder cancer suffer from a high rate of tumor recurrence. Thus, new approaches and agents to improve quality of life and survival still need to be developed. The objective of the present study was to evaluate the effect and underlying mechanisms of boldine, an aporphine alkaloid of Peumus boldus, on bladder cancer proliferation and cell death. METHODS: Sulforhodamine B assay, Tetrazolium reduction assay, Flow Cytometry Analysis, Ecto-5'-nucleotidase activity and Western blot assay were performed. RESULTS: The results showed that boldine was able to reduce cell viability and cell proliferation in T24 cells. In addition, boldine arrests the cell cycle at G2/M-phase and cause cell death by apoptosis. Boldine-induced inhibition of cell growth and cell cycle arrest appears to be linked to inactivation of extracellular signal-regulated kinase protein (ERK). Additionally, the efficacy of boldine in apoptosis-induced in T24 cells is correlated with modulation of AKT (inactivation) and glycogen synthase kinase-3ß (GSK-3ß) (activation) proteins. CONCLUSIONS: The present findings may, in part, explain the therapeutic effects of boldine for treatment of urinary bladder cancer.
