Anticancer activity of beta adrenoblockers in non-small cell lung cancer cell lines A549 and H1299

Abstract

Introduction Beta adrenoblockers (also known as beta blockers) are a class of drugs used for the treatment of cardiovascular diseases and glaucoma. The first evidence of beta adrenergic receptor signalling pathway involvement in lung cancer development appeared in 1989 [1]. Moreover, beta adrenoblocker application is associated with the increased survival outcomes in patients with non-small cell lung cancer [2]. According to recent studies, beta blockers also possess anticancer activity in pancreatic, breast, colorectal, prostate and ovarian cancer [4-6]. Materials and methods The aim of our research was to investigate the anticancer activity of seven beta adrenoblockers (β1 selective: atenolol, metoprolol, esmolol, betaxolol, and non-selective compounds: propranolol, timolol, pindolol) in nonsmall cell lung cancer cell lines A549 and H1299. Compound effect on cell viability was established by MTT assay. The activity of beta adrenoblockers on clonogenicity of lung cancer cells was tested by evaluating the effect on the colony-forming ability. The type of cell death was evaluated by cell staining with Hoechst 33342 and Propidium iodide. Results and discussion Propranolol and betaxolol inhibited lung cancer cell growth. Among tested compounds propranolol had the greatest effect on cell viability (EC50 values after 72 h on A549 and H1299 cell lines were 119.3 ± 12.7 μM and 98.8 ± 10.3 μM, respectively). Betaxolol effect on cell viability was similar in both cell lines (EC50 was 251.33 ± 14.61 μM against A549 and 252.23 ± 7.62 μM against H1299). Other compounds did not reduce the cancer cell viability at concentrations less than 500 μM. Propranolol and betaxolol at concentrations equal to 90% of calculated EC50 values completely suppressed cell colony formation. Betaxolol possessed this effect on A549 cell clonogenicity at a concentration equal to 10% from EC50 value, while the rest of the compounds did not induce statistically significant effect. The