Er–mitochondria calcium flux by β-sitosterol promotes cell death in ovarian cancer

Hyocheol Bae, Sunwoo Park, Jiyeon Ham, Jisoo Song, Taeyeon Hong, Jin Hee Choi, Gwonhwa Song, Whasun Lim

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Phytosterols, which are derived from plants, have various beneficial physiological effects, including anti-hypercholesterolemic, anti-inflammatory, and antifungal activities. The anticancer activities of natural products have attracted great attention, being associated with a low risk of side effects and not inducing antineoplastic resistance. β-sitosterol, a phytosterol, has been reported to have anticancer effects against fibrosarcoma and colon, breast, lung, and prostate cancer. However, there are no reports of its activity against ovarian cancer. Therefore, we investigated whether β-sitosterol shows anticancer effects against ovarian cancer using human ovarian cancer cell lines. We confirmed that β-sitosterol induced the apoptosis of ovarian cancer cells and suppressed their pro-liferation. It triggered pro-apoptosis signals and the loss of mitochondrial membrane potential, en-hanced the generation of reactive oxygen species and calcium influx through the endoplasmic re-ticulum–mitochondria axis, and altered signaling pathways in human ovarian cancer cells. In addi-tion, we observed inhibition of cell aggregation, suppression of cell growth, and decreased cell mi-gration in ovarian cancer cells treated with β-sitosterol. Further, our data obtained using ovarian cancer cells showed that, in combination with standard anti-cancer drugs, β-sitosterol demonstrated synergistic anti-cancer effects. Thus, our study suggests that β-sitosterol may exert anti-cancer effects against ovarian cancer in humans.

Original languageEnglish
Article number1583
JournalAntioxidants
Volume10
Issue number10
DOIs
Publication statusPublished - 2021 Oct

Bibliographical note

Funding Information:
Funding: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1A2C2089914, 2020R1I1A1A01067648, 2021R1A2C2005841, and 2021R1C1C1009807)

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • 3D spheroid
  • Apoptosis
  • ER-mitochondria calcium flux
  • Ovarian cancer
  • β-sitosterol

ASJC Scopus subject areas

  • Food Science
  • Physiology
  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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