title: Antiproliferative effects of β-blockers on human colorectal cancer cells.
abstract: 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 α- and β-adrenergic receptors (AR). Colon cancer cells express β-AR, and their activation has been implicated in carcinogenesis and tumor progression. Interest concerning the efficacy of β-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 β-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 µM) for 12 or 24 h. The tested AR agonists revealed proliferative effects on HT-29 cells. In order to study the effect of several β-blockers following proliferation induced by AR activation, the cells were treated with propranolol (PRO; 50 µM), carvedilol (CAR; 5 µM), atenolol (ATE; 50 µM), or ICI 118,551 (ICI; 5 µM) for 45 min prior, and simultaneously, to incubation with each of the AR agonists, AD and ISO, both at 1 and 10 µM. The results suggested that adrenergic activation plays an important role in colon cancer cell proliferation, most probably through β-AR. The β-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 β-blockers, may contribute to identifying promising strategies in cancer treatment.
authors: Department of Biochemistry, Faculty of Medicine of The University of Porto, Porto, Portugal.
authors: M
authors: M
authors: Coelho
authors: Department of Biochemistry, Faculty of Medicine of The University of Porto, Porto, Portugal.
authors: M
authors: M
authors: Moz
authors: Department of Biochemistry, Faculty of Medicine of The University of Porto, Porto, Portugal.
authors: G
authors: G
authors: Correia
authors: Molecular Oncology Group, Portuguese Institute of Oncology of Porto, Porto, Portugal.
authors: A
authors: A
authors: Teixeira
authors: Molecular Oncology Group, Portuguese Institute of Oncology of Porto, Porto, Portugal.
authors: R
authors: R
authors: Medeiros
authors: Department of Biochemistry, Faculty of Medicine of The University of Porto, Porto, Portugal.
authors: L
authors: L
authors: Ribeiro
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D000077261:Carvedilol; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D000077261:Carvedilol; C026777:ICI 118551; D001262:Atenolol; D011433:Propranolol; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine