Title : Anti-cancer effect of Tuberatolide B in MDA-MB-231 cells through induction of ROS and inhibition of STAT3 pathway
Tuberatolide B (TTB, C27H34O4) is a diastereomeric meroterpenoid isolated from the Korean marine algae Sargassum macrocarpum. However, the anticancer effects of TTB remain unknown. In this study, we demonstrate that TTB inhibits tumor growth in breast, lung, colon, prostate, and cervical cancer cells. To examine the mechanism by which TTB suppresses cell growth, we determined the effect of TTB on apoptosis, ROS generation, DNA damage, and signal transduction. TTB induced ROS production in MDA-MB-231, A549, and HCT116 cells. Moreover, TTB enhanced DNA damage by inducing H2AX foci formation and the phosphorylation of DNA damage-related proteins such as Chk2 and H2AX. Furthermore, TTB selectively inhibited STAT3 activation, which resulted in a reduction in cyclin D1, MMP-9, survivin, VEGF, and IL-6. In addition, TTB-induced ROS generation caused STAT3 inhibition, DNA damage, and apoptotic cell death. Therefore, TTB suppresses cancer progression by promoting ROS-mediated inhibition of STAT3 signaling, suggesting that TTB is useful for the treatment of cancer.
Audience take away:
• Cancer still remains a deadly disease and has a high incidence and death rate worldwide and targeted cancer therapeutic agents are developed for cancer patients for a long time.
• Tuberatolide B on diverse cancer cells result from the induction of ROS-mediated apoptosis by inhibiting of STAT3 phosphorylation and enhancing of DNA damage.
• Tuberatolide B might be an effective and useful chemotherapy agent against cancer.