Tuberatolide B Suppresses Cancer Progression by Promoting ROS-Mediated Inhibition of STAT3 Signaling

Abstract

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 γH2AX 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.

Anticancer Activities of Meroterpenoids Isolated from the Brown Alga Cystoseira usneoides against the Human Colon Cancer Cells HT-29

“…This finding was consistent with previous reports that demonstrated the apoptotic effects caused by various AMTs [29,30]. In particular, the AMT tuberatolide B, isolated from the alga Sargassum macrocarpum [31], has been shown to inhibit the viability of various cancer cell lines, including breast cancer (MDA-MB-231), lung cancer (A549), and colon cancer (HCT116), by inducing apoptotic cell death, and sargachromanol E, from Sargassum siliquastrum, has been reported to induce apoptosis in the colon cancer cell line HL-60 [32]. On the other hand, in the last years a variety of algal terpenoids have been reported to induce apoptosis in several cancer cells, including HT-29 [33], Jurkat leukemic cells [34], melanoma B16F10 cells [35,36], and human TNBC cells [37].…”

Marine natural products

“…The carotenoid pigment, fucoxanthin shows antiproliferative effects on non small cell lung cancer, 354 and inhibits the growth of colon cancer cells, 355 fucoxanthinol inhibits human colorectal cancer tumorigenicity, 356 tuberatolide B inhibits the growth of breast, lung, colon, prostate and cervical cancers. 357 Fucoxanthin also weakly inhibits monoamine oxidase A and B, prevents H 2 O 2 -induced neuronal apoptosis 358 and is antioxidant and antihypertensive. 359 Molecular modelling docking studies have helped to identify the binding mode of three very weakly active thrombin inhibitors pachydictyol A, isopachydictyol A and dichotomanol.…”

Algae-Derived Bioactive Compounds with Anti-Lung Cancer Potential

“…Tuberatolide B was isolated for the first time from the Korean Sargassum macrocarpum and identified as diastereomeric meroterpenoid that acts as a Farnesoid X receptor (FXR) antagonist [81]. Recently, Choi et al [38] proved that TTB induced the ROS production leading to STAT3 inhibition, DNA damage, and apoptotic cell death. Therefore, TTB suppresses cancer progression by promoting ROS-mediated inhibition of STAT3 signaling.…”

“…Choi et al [38] proved that tuberatolide B inhibits lung cancer growth via the histone H2AX protein, which is important in the DNA damage response (DDR) pathway. The formation of γH2AX foci on double stranded DNA activates the DDR pathway.…”