title: Hyperforin Inhibits Cell Growth by Inducing Intrinsic and Extrinsic Apoptotic Pathways in Hepatocellular Carcinoma Cells.
abstract: The aim of the present study was to investigate the antitumor effect and mechanism of action of hyperforin in hepatocellular carcinoma (HCC) SK-Hep1 cells in vitro. Cells were treated with different concentrations of hyperforin for different periods of time. Effects of hyperforin on cell viability, apoptosis signaling, and expression of anti-apoptotic and proliferative proteins [cellular FLICE-like inhibitory protein (c-FLIP), X-linked inhibitor of apoptosis protein (XIAP), myeloid cell leukemia 1(MCL1), and cyclin-D1] were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and western blotting. Hyperforin significantly inhibited cell viability and expression of anti-apoptotic and proliferative proteins. We also found that hyperforin significantly induced accumulation of cells in sub-G1phase, loss of mitochondrial membrane potential, and increased levels of active caspase-3, and caspase-8. Taken together, our findings indicate that hyperforin triggers inhibition of tumor cell growth by inducing intrinsic and extrinsic apoptotic pathways in HCC SK-Hep1 cells.
authors.affiliation: Department of Radiation Oncology, National Yang-Ming University Hospital, Yilan, Taiwan, R.O.C.|Cancer Medical Care Center, National Yang-Ming University Hospital, Yilan, Taiwan, R.O.C.|Department of Radiological Technology, Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C.
authors.forename: I-Tsang
authors.initials: IT
authors.lastname: Chiang
authors.affiliation: Department of Psychiatry, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan, R.O.C.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan, R.O.C.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Tseng
authors.affiliation: Cancer Medical Care Center, National Yang-Ming University Hospital, Yilan, Taiwan, R.O.C.|Department of Pathology, National Yang-Ming University Hospital, Yilan, Taiwan, R.O.C.
authors.forename: Yen-Chung
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Radiation Oncology, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Kuo
authors.affiliation: Department of Laboratory Medicine, Changhua Christian Hospital, Changhua Christian Medical Foundation, Changhua, Taiwan, R.O.C.
authors.forename: Bi-Jhih
authors.initials: BJ
authors.lastname: Chen
authors.affiliation: Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan, R.O.C.
authors.forename: Mao-Chi
authors.initials: MC
authors.lastname: Weng
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, College of Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C. 11313@ymuh.ym.edu.tw buddhistlearning@gmail.com.|Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shuang-Ho Hospital, New Taipei, Taiwan, R.O.C.
authors.forename: Hwai-Jeng
authors.initials: HJ
authors.lastname: Lin
authors.affiliation: Cancer Medical Care Center, National Yang-Ming University Hospital, Yilan, Taiwan, R.O.C. 11313@ymuh.ym.edu.tw buddhistlearning@gmail.com.|National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.|Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan, R.O.C.
authors.forename: Wei-Shu
authors.initials: WS
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013729:Terpenes / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D013729:Terpenes; D010696:Phloroglucinol; C001654:hyperforin
keywords: Hepatocellular carcinoma; apoptosis; hyperforin