Characterization of Ethanol-Induced Enhancement of Human Epidermal Growth Factor Receptor 2 Mediated Cardiotoxic Interactions

Abstract

Trastuzumab (TZB), a targeted therapy for HER2-positive breast cancer, is associated with cardiotoxicity driven by oxidative stress and disrupted autophagy. Ethanol, widely consumed among cancer patients, also induces cardiomyocyte damage through increased reactive oxygen species (ROS) and calcium dysregulation. This study investigates whether ethanol amplifies TZB-induced cardiotoxicity in HER2-overexpressing rat cardiomyocytes. We hypothesized that ethanol exposure exacerbates ROS generation, suppresses antioxidant enzymes such as heme oxygenase-1 (HO-1), Catalase, and Glutathione, and inhibits autophagy marker LC3B. H9c2 cardiomyoblasts were treated with ethanol (1%) for 24 hours and analyzed via immunofluorescence and western blotting. Ethanol significantly increased HER2 expression and decreased HO-1 levels, suggesting a potential mechanism for exacerbated cardiotoxicity. These findings provide novel insight into how ethanol may worsen the cardiac side effects of TZB and highlight the need for monitoring alcohol consumption in cancer patients undergoing HER2-targeted therapy.