PMID- 33288572 OWN - NLM STAT- MEDLINE DCOM- 20201221 LR - 20201221 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 40 IP - 12 DP - 2020 Dec TI - Hypoxia-inducible Factor-1alpha Suppression in Ovarian Clear-cell Carcinoma Cells by Silibinin Administration. PG - 6791-6798 LID - 10.21873/anticanres.14702 [doi] AB - BACKGROUND/AIM: Advanced ovarian clear-cell carcinoma (CCC) fails to respond to standard chemotherapy, and has a poor prognosis. Since hypoxia-inducible factor-1 (HIF-1) stimulates various genes involved in cancer, we aimed to examine the efficacy of silibinin, an active component of milk thistle belonging to Asteraceae, in suppressing HIF-1 activity, and elucidate the underlying mechanism in human CCC cell lines. MATERIALS AND METHODS: Human ovarian CCC cell lines HAC-2, OVISE, and RMG-1 were treated with 500 muM silibinin for 4 h under normoxic and hypoxic conditions. Using DNA microarray, we analysed genes whose expression modulated more than 2-fold in response to hypoxia, whereas HIF-1alpha expression was measured using ELISA. RESULTS: Silibinin treatment decreased HIF-1alpha protein in all cell lines, and eIF4E2 and RPS6 mRNA in HAC-2 and RMG-1 cells. CONCLUSION: Silibinin suppressed HIF-1alpha protein under hypoxic conditions in CCC cell lines and could be a potential anti-cancer drug. CI - Copyright (c) 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. FAU - Miyazawa, Mariko AU - Miyazawa M AD - Department of Obstetrics and Gynaecology, Tokai University School of Medicine, Kanagawa, Japan. FAU - Yasuda, Masanori AU - Yasuda M AD - Department of Pathology, Saitama Medical University International Medical Centre, Saitama, Japan; m_yasuda@saitama-med.ac.jp. FAU - Miyazawa, Masaki AU - Miyazawa M AD - Department of Obstetrics and Gynaecology, Tokai University School of Medicine, Kanagawa, Japan. FAU - Ogane, Naoki AU - Ogane N AD - Department of Pathology, Kanagawa Prefectural Ashigarakami Hospital, Kanagawa, Japan. FAU - Katoh, Tomomi AU - Katoh T AD - Department of Pathology, Saitama Medical University International Medical Centre, Saitama, Japan. FAU - Yano, Mitsutake AU - Yano M AD - Department of Pathology, Saitama Medical University International Medical Centre, Saitama, Japan. AD - Department of Obstetrics and Gynaecology, Oita University Faculty of Medicine, Oita, Japan. FAU - Hirasawa, Takeshi AU - Hirasawa T AD - Department of Obstetrics and Gynaecology, Tokai University School of Medicine, Kanagawa, Japan. FAU - Mikami, Mikio AU - Mikami M AD - Department of Obstetrics and Gynaecology, Tokai University School of Medicine, Kanagawa, Japan. FAU - Ishimoto, Hitoshi AU - Ishimoto H AD - Department of Obstetrics and Gynaecology, Tokai University School of Medicine, Kanagawa, Japan. LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (Biomarkers) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 4RKY41TBTF (Silybin) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) SB - IM MH - Adenocarcinoma, Clear Cell/drug therapy/genetics/*metabolism MH - Antineoplastic Agents, Phytogenic/*administration & dosage MH - Biomarkers MH - Cell Hypoxia MH - Cell Line, Tumor MH - Female MH - Gene Expression Regulation, Neoplastic/drug effects MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists & inhibitors/*metabolism MH - L-Lactate Dehydrogenase/metabolism MH - Ovarian Neoplasms/drug therapy/genetics/*metabolism MH - Signal Transduction/drug effects MH - Silybin/*administration & dosage OTO - NOTNLM OT - HIF-1alpha OT - RPS6 OT - eIF4E OT - ovarian clear-cell carcinoma OT - silibinin EDAT- 2020/12/09 06:00 MHDA- 2020/12/22 06:00 CRDT- 2020/12/08 05:39 PHST- 2020/10/19 00:00 [received] PHST- 2020/11/09 00:00 [revised] PHST- 2020/11/13 00:00 [accepted] PHST- 2020/12/08 05:39 [entrez] PHST- 2020/12/09 06:00 [pubmed] PHST- 2020/12/22 06:00 [medline] AID - 40/12/6791 [pii] AID - 10.21873/anticanres.14702 [doi] PST - ppublish SO - Anticancer Res. 2020 Dec;40(12):6791-6798. doi: 10.21873/anticanres.14702.