The Potent Cytotoxic and Oxidative Effects of beta-2 Selective ICI-118,551 on Breast Adenocarcinoma Cell Lines with Different Aggressiveness

Abstract

Objective: Beta-blockers are a group of drugs used in the treatment of cardiovascular diseases. On the other hand, the potential anticancer effects of these drugs have become increasingly important in recent two decades. In this paper, the effects of beta-1 selective esmolol, beta-2 selective ICI-118,551 and non-selective nadolol on breast cancer cell lines with different aggressiveness were investigated for the first time. Methods: A standard spectrophotometricMTT assay was used to determine cell viability. Catalase activities and malondialdehyde levels were measured spectrophotometrically based on the reduction of absorbance resulted from hydrogen peroxide decomposition and the formation of thiobarbituric acid - malondialdehyde product, respectively. Results: It was found that beta-2 selective ICI-118,551 was the most effective one among investigated blockers against MCF-7 and MDA-MB-231 cell lines. Additionally, it was seen that 50-150 mu M ICI-118,551 treatment for 48 hours significantly changed catalase activities and malondialdehyde levels in both breast cancer cell lines in favour of radical production. Conclusion: The obtained results showed that beta-2 adrenergic receptor specific antagonism plays a significant role in beta-blocker induced breast cancer cell death. The outstanding suppression in catalase activities and concomitant increase in radical levels appear to contribute to potent cytotoxic effect of ICI-118,551 on breast adenocarcinoma. Consequently, it can be clearly interpreted that ICI-118,551 may be a valuable option in the treatment of breast cancer.