Anti-tumoral effect of beta-blockers on prostate and bladder cancer cells via mitogen-activated protein kinase pathways.

Abstract

The incidence of prostate cancer in the world is increasing every year. Death caused by prostate cancer is increased by 13% in men between 1980 and 2005. It is the second leading cause of cancer death in men after lung cancer. Bladder cancer is the second most common of urological malignancies. Most of the bladder cancers are treated with transurethral resection. Even great efforts have been made in the treatment of bladder cancer over the past years, it still remains as a major health problem. New therapeutic approaches are required to prevent the development and metastasis of these diseases. Experimental and clinical studies have shown potential beneficial effects of co-administration of beta-adrenergic receptor antagonists (beta-blockers) during cancer therapy. This study aimed to investigate the anti-tumor activity of beta-blockers on prostate and bladder cancer. Prostate and bladder cancer cell lines were cultured and treated with beta-blocker (propranolol). Then, protein levels and activity of apoptotic pathway mediators and mitogen-activated protein kinase (MAPK) pathway mediators were analyzed by ELISA. Propranolol treatment elevated the activity of caspase-3 and expression of bax, Wee1, GADD153 and apoptosis-inducing factor, but decreased bcl-2 which is an antiapoptotic protein. Propranolol treatment also inhibited ERK and JNK activity. This study showed that propranolol will help to inhibit prostate and bladder cancer by activating apoptotic pathway and by inhibiting MAPK pathway. This is the first study investigating the apoptotic effect of propranolol via MAPK on prostate and bladder cancer.