title: 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 algaeSargassum 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.
authors.affiliation: Jeju International Marine Science Center for Research & Education, Korea Institute of Ocean Science & Technology (KIOST), Jeju 63349, Korea. choiyk@kiost.ac.kr.
authors.forename: Youn Kyung
authors.initials: YK
authors.lastname: Choi
authors.affiliation: Jeju International Marine Science Center for Research & Education, Korea Institute of Ocean Science & Technology (KIOST), Jeju 63349, Korea. junseong@kiost.ac.kr.
authors.forename: Junseong
authors.initials: J
authors.lastname: Kim
authors.affiliation: Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02247, Korea. linkin1102@naver.com.
authors.forename: Kang Min
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02247, Korea. ehowlqk11@naver.com.
authors.forename: Yu-Jeong
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Jeju International Marine Science Center for Research & Education, Korea Institute of Ocean Science & Technology (KIOST), Jeju 63349, Korea. ramiz@kiost.ac.kr.
authors.forename: Bo-Ram
authors.initials: BR
authors.lastname: Ye
authors.affiliation: Jeju International Marine Science Center for Research & Education, Korea Institute of Ocean Science & Technology (KIOST), Jeju 63349, Korea. iskim9924@kiost.ac.kr.
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02247, Korea. epiko@khu.ac.kr.
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Ko
authors.affiliation: Division of Food Bioscience, and Korea Nokyong Research Center, Konkuk University, Chungju 380-701, Korea. leesh80@kku.ac.kr.
authors.forename: Seung-Hong
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Jeju International Marine Science Center for Research & Education, Korea Institute of Ocean Science & Technology (KIOST), Jeju 63349, Korea. dohkang@kiost.ac.kr.
authors.forename: Do-Hyung
authors.initials: DH
authors.lastname: Kang
authors.affiliation: Jeju International Marine Science Center for Research & Education, Korea Institute of Ocean Science & Technology (KIOST), Jeju 63349, Korea. sjheo@kiost.ac.kr.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Heo
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D018450:Disease Progression; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013729:Terpenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051034:Inhibitor of Apoptosis Proteins; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D013729:Terpenes; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1; D020780:Matrix Metalloproteinase 9
keywords: DNA damage; ROS; STAT3; cancer; tuberatolide B