Antiproliferative effects of β-blockers on human colorectal cancer cells

Colon cancer is the fourth and third most common cancer, respectively in men and women worldwide and its incidence is on the increase. Stress response has been associated with the incidence and development of cancer. The catecholamines (CA), adrenaline (AD) and noradrenaline (NA), are crucial mediators of stress response, exerting their effects through interaction with alpha- and beta-adrenergic receptors (AR). Colon cancer cells express beta-AR, and their activation has been implicated in carcinogenesis and tumor progression. Interest concerning the efficacy of beta-AR blockers as possible additions to cancer treatment has increased. The aim of this study was to investigate the effect of several AR agonists and beta-blockers following cell proliferation of HT-29 cells, a human colon adenocarcinoma cell line. For this purpose, HT-29 cells were incubated in the absence (control) or in the presence of the AR-agonists, AD, NA and isoprenaline (ISO) (0.1-100 mu M) for 12 or 24 h. The tested AR agonists revealed proliferative effects on HT-29 cells. In order to study the effect of several beta-blockers following proliferation induced by AR activation, the cells were treated with propranolol (PRO; 50 mu M), carvedilol (CAR; 5 mu M), atenolol (ATE; 50 mu M), or ICI 118,551 (ICI; 5 mu M) for 45 min prior, and simultaneously, to incubation with each of the AR agonists, AD and ISO, both at 1 and 10 mu M. The results suggested that adrenergic activation plays an important role in colon cancer cell proliferation, most probably through beta-AR. The beta-blockers under study were able to reverse the proliferation induced by AD and ISO, and some of these blockers significantly decreased the proliferation of HT-29 cells. The elucidation of the intracellular pathways involved in CA-induced proliferation of colon cancer cells, and in the reversion of this effect by beta-blockers, may contribute to identifying promising strategies in cancer treatment.