Abstract A009: Effects of commonly prescribed β-blockers on tobacco carcinogen induced reactive oxygen species in human non-tumorigenic lung epithelial cells

Abstract

Abstract Lung cancer is a detrimental disease to humans and tobacco smoking causes more than 80% of lung cancer deaths. Chemoprevention is currently the major strategy to prevent smoking related lung cancer deaths. Key components that contribute to tobacco carcinogenicity are benzo(a)pyrene [B(a)P] and its diol epoxide metabolite BPDE. The goal of this study is to evaluate the level of reactive oxygen species (ROS), a mediator for cellular DNA damage leading to cancer, when pre-treated with the β-blockers carvedilol and nebivolol, and the antioxidant resveratrol. B(a)P and BPDE were used to induce ROS in human lung epithelial cells (BEAS-2B). The non- fluorescent and non-polar 2’,7- dichlorofluorescein diacetate (DCFH-DA) probe was added to the cells. DCFH-DA was converted to DCFH in the cells by hydrolyzation of DCFH. ROS then induced the conversation of DCFH into 2,7-dichlorofluorescein (DCF). Florescence of DCF was measured by flow cytometry to detect ROS level. B(a)P at concentrations 10 and 100 μM failed to induce ROS while BPDE successfully induced ROS dose-dependently during our pilot study. As a result, different concentrations of BPDE(2 μM and 4 μM) were used to induce ROS. When BEAS-2B was pre-treated with resveratrol (50 μM), ROS was reduced by 42% compared to the cells treated with 2 μM BPDE alone. Additionally, there was a decrease in ROS when pre-treated with nebivolol and carvedilol (5 μM). Nebivolol reduced 52% and 64% of the ROS induced by BPDE 2 μM and 4 μM, respectively. Carvedilol reduced 31% and 10% of the ROS induced by BPDE 2 μM and 4 μM, respectively. These results suggest that some commonly used anti-hypertensive agents, such as the β-blockers , may block or reduce tobacco carcinogen induced ROS and thus can be used as chemopreventive agents for lung cancer. Citation Format: Jenny Lee, Ayaz Shahid, Ying Huang. Effects of commonly prescribed β-blockers on tobacco carcinogen induced reactive oxygen species in human non-tumorigenic lung epithelial cells [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A009.