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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

by 1,†, 1,†, 2, 2,* and 1,*
1
Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea
2
Department of Food and Nutrition, Kookmin University, Seoul 02707, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2020, 12(7), 640; https://doi.org/10.3390/pharmaceutics12070640
Received: 17 June 2020 / Revised: 2 July 2020 / Accepted: 4 July 2020 / Published: 7 July 2020
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. View Full-Text
Keywords: 4-methylumbelliferone; ovarian cancer; proliferation; endoplasmic reticulum stress; calcium homeostasis 4-methylumbelliferone; ovarian cancer; proliferation; endoplasmic reticulum stress; calcium homeostasis
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MDPI and ACS Style

An, G.; Park, S.; Lee, M.; Lim, W.; Song, G. 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. Pharmaceutics 2020, 12, 640. https://doi.org/10.3390/pharmaceutics12070640

AMA Style

An G, Park S, Lee M, Lim W, Song G. 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. Pharmaceutics. 2020; 12(7):640. https://doi.org/10.3390/pharmaceutics12070640

Chicago/Turabian Style

An, Garam, Sunwoo Park, Minkyoung Lee, Whasun Lim, and Gwonhwa Song. 2020. "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" Pharmaceutics 12, no. 7: 640. https://doi.org/10.3390/pharmaceutics12070640

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