Antiproliferative effect of 4-methylumbelliferone in epithelial ovarian cancer cells is mediated by disruption of intracellular homeostasis and regulation of PI3K/AKT and mapk signaling

Garam An, Sunwoo Park, Minkyoung Lee, Whasun Lim, Gwonhwa Song

Research output: Contribution to journalArticlepeer-review

Abstract

Ovarian cancer has a high mortality rate and high resistance to chemotherapy. Thus, many studies are currently assessing the ability of natural products to induce ovarian cancer cell death. A coumarin derivative, 4-methylumbelliferone (4-MU), has been reported to have anti-cancer effects on various cancers, but its effects on ovarian cancer are not fully understood. In this study, we identified the intracellular mechanism underlying the effects of 4-MU on epithelial ovarian cancer cells. Decreased ovarian cancer cell proliferation and an accumulation of cells in the G2/M phase were observed following 4-MU treatment. Moreover, 4-MU interfered with calcium homeostasis; induced endoplasmic reticulum stress in both cell lines; inhibited AKT and S6 phosphorylation; and increased ERK1/2, P38, and JNK phosphorylation. Furthermore, 4-MU and pharmacological inhibitors showed synergic effects in suppressing cell proliferation. Collectively, our current data indicate that antitumor effects of 4-MU could be appropriate for use as a therapeutic agent against epithelial ovarian cancer cells.

Original languageEnglish
Article number640
Pages (from-to)1-14
Number of pages14
JournalPharmaceutics
Volume12
Issue number7
DOIs
Publication statusPublished - 2020 Jul

Keywords

  • 4-methylumbelliferone
  • Calcium homeostasis
  • Endoplasmic reticulum stress
  • Ovarian cancer
  • Proliferation

ASJC Scopus subject areas

  • Pharmaceutical Science

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