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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
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408106/ https://www.ncbi.nlm.nih.gov/pubmed/32645961 http://dx.doi.org/10.3390/pharmaceutics12070640 |
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author | An, Garam Park, Sunwoo Lee, Minkyoung Lim, Whasun Song, Gwonhwa |
author_facet | An, Garam Park, Sunwoo Lee, Minkyoung Lim, Whasun Song, Gwonhwa |
author_sort | An, Garam |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7408106 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74081062020-08-25 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 An, Garam Park, Sunwoo Lee, Minkyoung Lim, Whasun Song, Gwonhwa Pharmaceutics Article 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. MDPI 2020-07-07 /pmc/articles/PMC7408106/ /pubmed/32645961 http://dx.doi.org/10.3390/pharmaceutics12070640 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article An, Garam Park, Sunwoo Lee, Minkyoung Lim, Whasun Song, Gwonhwa 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408106/ https://www.ncbi.nlm.nih.gov/pubmed/32645961 http://dx.doi.org/10.3390/pharmaceutics12070640 |
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