Sargassum macrocarpum suppresses cancer progression by inhibiting ROS-mediated STAT3 signaling pathway

Abstract

Tuberatolide B (TTB, C27H34O4), a diastereomeric meroterpenoids isolated from marine algae Sargassum macrocarpum. However, the anticancer effects of TTB are still unknown in cancer. In this study, we demonstrate that TTB inhibits tumor growth of breast cancer, lung cancer, colon cancer, prostate cancer, cervical cancer cells. To examine the mechanism action by TTB suppresses cell growth, we confirmed the effect of TTB on apoptosis, ROS generation, DNA damage and signal transduction. TTB induced ROS production of MDA-MB-231, A549 and HCT116 cells. Moreover, TTB enhanced DNA damage, inducing the γH2AX foci formation and phosphorylation of DNA damage-related protein expression levels such as Chk2 and H2AX. Furthermore, TTB selectively inhibited STAT3 activation, which resulted in a reduction of Cyclin D1, MMP-9, Survivin, VEGF and IL-6. In addition, TTB-induced ROS generation causes STAT3 inhibition, DNA damage and apoptotic cell death. Therefore, TTB suppresses cancer progression by inhibiting ROS-mediated STAT3 signaling pathway suggesting that TTB may be useful for treating cancer.wth of breast cancer, lung cancer, colon cancer, prostate cancer, cervical cancer cells. To examine the mechanism action by TTB suppresses cell growth, we confirmed the effect of TTB on apoptosis, ROS generation, DNA damage and signal transduction. TTB induced ROS production of MDA-MB-231, A549 and HCT116 cells. Moreover, TTB enhanced DNA damage, inducing the γH2AX foci formation and phosphorylation of DNA damage-related protein expression levels such as Chk2 and H2AX. Furthermore, TTB selectively inhibited STAT3 activation, which resulted in a reduction of Cyclin D1, MMP-9, Survivin, VEGF and IL-6. In addition, TTB-induced ROS generation causes STAT3 inhibition, DNA damage and apoptotic cell death. Therefore, TTB suppresses cancer progression by inhibiting ROS-mediated STAT3 signaling pathway suggesting that TTB may be useful for treating cancer.