title: Gomisin A enhances tumor necrosis factor-α-induced G1 cell cycle arrest via signal transducer and activator of transcription 1-mediated phosphorylation of retinoblastoma protein.
abstract: Gomisin A, a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra chinensis, has been reported as an anti-cancer substance. In this study, we investigated the effects of gomisin A on cancer cell proliferation and cell cycle arrest in HeLa cells. Gomisin A significantly inhibited cell proliferation in a dose-dependent manner after 72 h treatment, especially in the presence of tumor necrosis factor-α (TNF-α), due to cell cycle arrest in the G1 phase with the downregulation of cyclin D1 expression and Retinoblastoma (RB) phosphorylation. In addition, gomisin A in combination with TNF-α strongly suppressed the expression of signal transducer and activator of transcription 1 (STAT1). Inhibition of STAT1 pathways by a small-interfering RNA against STAT1 and AG490 Janus kinase (JAK) kinase inhibitor AG490 reduced the cyclin D1 expression and RB phosphorylation, indicating that JAK-mediated STAT1 activation is involved in gomisin A-induced G1 cell cycle arrest.
authors.affiliation: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930–0194, Japan.
authors.forename: Pornthip
authors.initials: P
authors.lastname: Waiwut
authors.forename: Myoung-Sook
authors.initials: MS
authors.lastname: Shin
authors.forename: Satoru
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D034242:Cyclooctanes / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D059585:G1 Phase Cell Cycle Checkpoints / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D010766:Phosphorylation; D016160:Retinoblastoma Protein; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D032141:Schisandra; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000970:Antineoplastic Agents; D034242:Cyclooctanes; D004149:Dioxoles; D004365:Drugs, Chinese Herbal; D017705:Lignans; D016160:Retinoblastoma Protein; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014409:Tumor Necrosis Factor-alpha; C033585:schizandrol B