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Research ArticleExperimental Studies

Hypoxia-inducible Factor-1α Suppression in Ovarian Clear-cell Carcinoma Cells by Silibinin Administration

MARIKO MIYAZAWA, MASANORI YASUDA, MASAKI MIYAZAWA, NAOKI OGANE, TOMOMI KATOH, MITSUTAKE YANO, TAKESHI HIRASAWA, MIKIO MIKAMI and HITOSHI ISHIMOTO
Anticancer Research December 2020, 40 (12) 6791-6798; DOI: https://doi.org/10.21873/anticanres.14702
MARIKO MIYAZAWA
1Department of Obstetrics and Gynaecology, Tokai University School of Medicine, Kanagawa, Japan
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MASANORI YASUDA
2Department of Pathology, Saitama Medical University International Medical Centre, Saitama, Japan;
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  • For correspondence: m_yasuda@saitama-med.ac.jp
MASAKI MIYAZAWA
1Department of Obstetrics and Gynaecology, Tokai University School of Medicine, Kanagawa, Japan
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NAOKI OGANE
3Department of Pathology, Kanagawa Prefectural Ashigarakami Hospital, Kanagawa, Japan
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TOMOMI KATOH
2Department of Pathology, Saitama Medical University International Medical Centre, Saitama, Japan;
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MITSUTAKE YANO
2Department of Pathology, Saitama Medical University International Medical Centre, Saitama, Japan;
4Department of Obstetrics and Gynaecology, Oita University Faculty of Medicine, Oita, Japan
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TAKESHI HIRASAWA
1Department of Obstetrics and Gynaecology, Tokai University School of Medicine, Kanagawa, Japan
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MIKIO MIKAMI
1Department of Obstetrics and Gynaecology, Tokai University School of Medicine, Kanagawa, Japan
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HITOSHI ISHIMOTO
1Department of Obstetrics and Gynaecology, Tokai University School of Medicine, Kanagawa, Japan
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Abstract

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 μM 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-1α expression was measured using ELISA. Results: Silibinin treatment decreased HIF-1α protein in all cell lines, and eIF4E2 and RPS6 mRNA in HAC-2 and RMG-1 cells. Conclusion: Silibinin suppressed HIF-1α protein under hypoxic conditions in CCC cell lines and could be a potential anti-cancer drug.

Key Words:
  • HIF-1α
  • silibinin
  • eIF4E
  • RPS6
  • ovarian clear-cell carcinoma
  • Received October 19, 2020.
  • Revision received November 9, 2020.
  • Accepted November 13, 2020.
  • Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 40 (12)
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December 2020
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Hypoxia-inducible Factor-1α Suppression in Ovarian Clear-cell Carcinoma Cells by Silibinin Administration
MARIKO MIYAZAWA, MASANORI YASUDA, MASAKI MIYAZAWA, NAOKI OGANE, TOMOMI KATOH, MITSUTAKE YANO, TAKESHI HIRASAWA, MIKIO MIKAMI, HITOSHI ISHIMOTO
Anticancer Research Dec 2020, 40 (12) 6791-6798; DOI: 10.21873/anticanres.14702

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Hypoxia-inducible Factor-1α Suppression in Ovarian Clear-cell Carcinoma Cells by Silibinin Administration
MARIKO MIYAZAWA, MASANORI YASUDA, MASAKI MIYAZAWA, NAOKI OGANE, TOMOMI KATOH, MITSUTAKE YANO, TAKESHI HIRASAWA, MIKIO MIKAMI, HITOSHI ISHIMOTO
Anticancer Research Dec 2020, 40 (12) 6791-6798; DOI: 10.21873/anticanres.14702
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Keywords

  • HIF-1α
  • silibinin
  • eIF4E
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  • ovarian clear-cell carcinoma
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