title: Adenanthin targets peroxiredoxin I/II to kill hepatocellular carcinoma cells.
abstract: Adenanthin, a natural diterpenoid isolated from the leaves of Isodon adenanthus, has recently been reported to induce leukemic cell differentiation by targeting peroxiredoxins (Prx) I and II. On the other hand, increasing lines of evidence propose that these Prx proteins would become potential targets to screen drugs for the prevention and treatment of solid tumors. Therefore, it is of significance to explore the potential activities of adenanthin on solid tumor cells. Here, we demonstrate that Prx I protein is essential for the survival of hepatocellular carcinoma (HCC) cells, and adenanthin can kill these malignant liver cells in vitro and xenografts. We also show that the cell death-inducing activity of adenanthin on HCC cells is mediated by the increased reactive oxygen species (ROS) levels. Furthermore, the silencing of Prx I or Prx II significantly enhances the cytotoxic activity of adenanthin on HCC, whereas the ectopic expression of Prx I and Prx II but not their mutants of adenanthin-bound cysteines can rescue adenanthin-induced cytotoxicity in Prxs-silenced HCC cells. Taken together, our results propose that adenanthin targets Prx I/II to kill HCC cells and its therapeutic significance warrants to be further explored in HCC patients.
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
authors.forename: J-K
authors.initials: JK
authors.lastname: Hou
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai, China.
authors.forename: W
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai, China.
authors.forename: Z-W
authors.initials: ZW
authors.lastname: Yan
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai, China.
authors.forename: M-H
authors.initials: MH
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Yunnan, China.
authors.forename: W-L
authors.initials: WL
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Yunnan, China.
authors.forename: H-D
authors.initials: HD
authors.lastname: Sun
authors.affiliation: 1] Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China [2] Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai, China [3] State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, SJTU-SM, Shanghai, 200032, China.
authors.forename: G-Q
authors.initials: GQ
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D045786:Diterpenes, Kaurane / Q000627:therapeutic use / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D037602:Isodon / Q000737:chemistry / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018384:Oxidative Stress / Q000187:drug effects; D054464:Peroxiredoxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018515:Plant Leaves / Q000737:chemistry / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D045786:Diterpenes, Kaurane; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C000600164:adenanthin; D054464:Peroxiredoxins