Rikkunshito attenuates induction of epithelial-mesenchymal switch via activation of Sirtuin1 in ovarian cancer cells

Ranka Kanda; Yuko Miyagawa; Osamu Wada-Hiraike; Haruko Hiraike; Shiho Fukui; Kazunori Nagasaka; Eiji Ryo; Tomoyuki Fujii; Yutaka Osuga; Takuya Ayabe

doi:10.1507/endocrj.EJ19-0368

ORIGINAL

Rikkunshito attenuates induction of epithelial-mesenchymal switch via activation of Sirtuin1 in ovarian cancer cells

Ranka Kanda, Yuko Miyagawa, Osamu Wada-Hiraike, Haruko Hiraike, Shiho Fukui, Kazunori Nagasaka, Eiji Ryo, Tomoyuki Fujii, Yutaka Osuga, Takuya Ayabe

Author information

Ranka Kanda
Department of Obstetrics and Gynecology, Teikyo University School of Medicine, Tokyo, Japan
Yuko Miyagawa
Department of Obstetrics and Gynecology, Teikyo University School of Medicine, Tokyo, Japan
Osamu Wada-Hiraike
Department of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan
Haruko Hiraike
Department of Obstetrics and Gynecology, Teikyo University School of Medicine, Tokyo, Japan
Shiho Fukui
Department of Obstetrics and Gynecology, Teikyo University School of Medicine, Tokyo, Japan
Kazunori Nagasaka
Department of Obstetrics and Gynecology, Teikyo University School of Medicine, Tokyo, Japan
Eiji Ryo
Department of Obstetrics and Gynecology, Teikyo University School of Medicine, Tokyo, Japan
Tomoyuki Fujii
Department of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan
Yutaka Osuga
Department of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan
Takuya Ayabe
Department of Obstetrics and Gynecology, Teikyo University School of Medicine, Tokyo, Japan

Keywords: Traditional Japanese herbal medicine, Rikkunshito, Ghrelin, Sirtuin1, Epithelial-mesenchymal transition

JOURNAL FREE ACCESS FULL-TEXT HTML

2020 Volume 67 Issue 4 Pages 379-386

DOI https://doi.org/10.1507/endocrj.EJ19-0368

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Abstract

Rikkunshito, a traditional Japanese herbal medicine, improves appetite via activation of gastrointestinal hormone ghrelin pathway. The function of ghrelin is mediated by growth hormone secretagogue receptor (GHSR1a), and ghrelin has been known to possess diverse physiological functions including growth suppression of some cancer cells. Considering that increased ghrelin signaling by Rikkunshito could enhance sirtuin1 (SIRT1) activity in nervous system, we aimed to investigate the effect of Rikkunshito in ovarian cancer cells. Ovarian cancer cell lines were treated with Rikkunshito, and cellular viability, gene expressions and epithelial-mesenchymal transition (EMT) status were investigated. To investigate the involvement of SIRT1 by Rikkunshito in SKOV3 cancer cells, endogenous expression of SIRT1 was depleted using small interfering RNA (siRNA). Treatment with Rikkunshito elevated ghrelin, GHSR1a and SIRT1, while cellular viability was decreased. The treatment of Rikkunshito also inhibited cellular migration and invasion status in a dose-dependent manner, and these effects were translated to the enhanced EMT status, although the role of SIRT1 was not determined. Our study revealed a novel function of Rikkunshito in enhancing EMT status of ovarian cancer cells. Therefore, we would like to propose that Rikkunshito may be used as a novel adjunctive therapy in chemotherapy of ovarian cancer because platinum-based chemotherapy frequently used for the treatment of ovarian cancer inevitably impairs appetite.

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