induction of apoptotic cell death through activating ROS-mediated inhibitionof STAT3 signaling pathway by tuberatolide B

Abstract

Cancer still remains a deadly disease and has a high incidence and death rate worldwide. In addition, ROS are generated by the metabolism of oxygen in normal cells and have critical roles in homeostasis and cell signaling. However cancer is caused by abnormal ROS generation. Therefore, diverse chemotherapeutic agents that increase ROS generation have been studied for cancer treatment. Tuberatolide B (C27H34O4) is a diastereomeric meroterpenoid isolated from the Korean marine algae Sargassum macrocarpum. However, the anticancer effects of Tuberatolide B remain unknown. In this study, we demonstrate that Tuberatolide B inhibits tumor growth in breast, lung, colon, prostate, and cervical cancer cells. Tuberatolide B suppressed cancer cell viability (breast cancer, lung cancer, colon cancer, prostate cancer, cervical cancer). In addition, Tuberatolide B did not affect normal monkey kidney epithelial cell viabilities. Tuberatolide B enhanced DNA damage and ROS generation and inhibited STAT3 activation. In addition, TTB-induced ROS generation caused STAT3 inhibition, DNA damage, and apoptotic cell death. Therefore, Tuberatolide B inhibits cancer development by inducing ROS-mediated suppression of STAT3 signaling, suggesting that TTB is useful for the treatment of cancer caused by abnormal ROS generation. Therefore, diverse chemotherapeutic agents that increase ROS generation have been studied for cancer treatment. Tuberatolide B (C27H34O4) is a diastereomeric meroterpenoid isolated from the Korean marine algae Sargassum macrocarpum. However, the anticancer effects of Tuberatolide B remain unknown. In this study, we demonstrate that Tuberatolide B inhibits tumor growth in breast, lung, colon, prostate, and cervical cancer cells. Tuberatolide B suppressed cancer cell viability (breast cancer, lung cancer, colon cancer, prostate cancer, cervical cancer). In addition, Tuberatolide B did not affect normal monkey kidney epithelial cell viabilities. Tuberatolide B enhanced DNA damage and ROS generation and inhibited STAT3 activation. In addition, TTB-induced ROS generation caused STAT3 inhibition, DNA damage, and apoptotic cell death. Therefore, Tuberatolide B inhibits cancer development by inducing ROS-mediated suppression of STAT3 signaling, suggesting that TTB is useful for the treatment of cancer