POTENTIAL MODULATION OF CANCER PROGRESSION BY MARINE ORGANISM-DERIVED COMPOUNDS

Abstract

Cancer still remains a deadly disease and has highest incidence and death rate in worldwide. Unlike normal cells, cancer cells has some characteristics such as sustaining proliferative signaling, evading growth suppressors, activating invasion and metastasis, enabling replicative immortality, inducing angiogenesis and resisting cell death. Therefore, targeted cancer therapeutic agents are developed for cancer patients for a long time. Especially, marine organism-derived compounds have shown anti-cancer effects with no or less side effects compared to other anti-cancer therapeutics including chemical compounds and targeting antibodies. Therefore, we examined anti-cancer effects of 36 kinds of marine organism-derived compounds on various types of cancer cells. Especially, Tuberatolide B (TTB, C27H34O4) much strongly inhibited cancer cell viability compared to other compounds. 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 generion and metastasis, enabling replicative immortality, inducing angiogenesis and resisting cell death. Therefore, targeted cancer therapeutic agents are developed for cancer patients for a long time. Especially, marine organism-derived compounds have shown anti-cancer effects with no or less side effects compared to other anti-cancer therapeutics including chemical compounds and targeting antibodies. Therefore, we examined anti-cancer effects of 36 kinds of marine organism-derived compounds on various types of cancer cells. Especially, Tuberatolide B (TTB, C27H34O4) much strongly inhibited cancer cell viability compared to other compounds. 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 gener