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Three Combined Treatments, a Novel HDAC Inhibitor OBP-801/YM753, 5-Fluorouracil, and Paclitaxel, Induce G(2) Phase Arrest Through the p38 Pathway in Human Ovarian Cancer Cells
Ovarian cancer is the most lethal disease among gynecological malignancies. More effective therapy is required to counter high recurrence rates and chemotherapy resistance. We investigated the efficacy and molecular mechanisms of three combined treatments (TCTs)—a novel histone deacetylase (HDAC) in...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Cognizant Communication Corporation
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841106/ https://www.ncbi.nlm.nih.gov/pubmed/28117030 http://dx.doi.org/10.3727/096504017X14850164661097 |
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author | Akiyama, Makoto Sowa, Yoshihiro Taniguchi, Tomoyuki Watanabe, Motoki Yogosawa, Shingo Kitawaki, Jo Sakai, Toshiyuki |
author_facet | Akiyama, Makoto Sowa, Yoshihiro Taniguchi, Tomoyuki Watanabe, Motoki Yogosawa, Shingo Kitawaki, Jo Sakai, Toshiyuki |
author_sort | Akiyama, Makoto |
collection | PubMed |
description | Ovarian cancer is the most lethal disease among gynecological malignancies. More effective therapy is required to counter high recurrence rates and chemotherapy resistance. We investigated the efficacy and molecular mechanisms of three combined treatments (TCTs)—a novel histone deacetylase (HDAC) inhibitor OBP-801/YM753, 5-fluorouracil (5-FU), and paclitaxel (PTX)—in human ovarian cancer SKOV-3 and OVCAR-3 cells. The inhibition of cell growth was stronger with TCTs than with each single agent and with two combined treatments. The TCTs significantly induce G(2) phase arrest in both cell lines. We then analyzed the molecular mechanisms and found that the TCTs increased the phosphorylation of p38 (Thr180/Tyr182), decreased the expression of CDC25C, and increased the phosphorylation of CDC2 (Tyr15), an inactive form of CDC2. To examine the responsibilities of the p38 pathway for G(2) phase arrest induced by the TCTs, we employed the p38 inhibitor SB203580. SB203580 inhibited G(2) phase arrest, suppression of CDC25C, and phosphorylation of CDC2 (Tyr15) induced by the TCTs. These results suggest that the TCTs can induce G(2) phase arrest through activation of the p38 signaling pathway. We therefore believe that this combination is promising as a novel therapeutic strategy against ovarian cancer. |
format | Online Article Text |
id | pubmed-7841106 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cognizant Communication Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-78411062021-02-16 Three Combined Treatments, a Novel HDAC Inhibitor OBP-801/YM753, 5-Fluorouracil, and Paclitaxel, Induce G(2) Phase Arrest Through the p38 Pathway in Human Ovarian Cancer Cells Akiyama, Makoto Sowa, Yoshihiro Taniguchi, Tomoyuki Watanabe, Motoki Yogosawa, Shingo Kitawaki, Jo Sakai, Toshiyuki Oncol Res Article Ovarian cancer is the most lethal disease among gynecological malignancies. More effective therapy is required to counter high recurrence rates and chemotherapy resistance. We investigated the efficacy and molecular mechanisms of three combined treatments (TCTs)—a novel histone deacetylase (HDAC) inhibitor OBP-801/YM753, 5-fluorouracil (5-FU), and paclitaxel (PTX)—in human ovarian cancer SKOV-3 and OVCAR-3 cells. The inhibition of cell growth was stronger with TCTs than with each single agent and with two combined treatments. The TCTs significantly induce G(2) phase arrest in both cell lines. We then analyzed the molecular mechanisms and found that the TCTs increased the phosphorylation of p38 (Thr180/Tyr182), decreased the expression of CDC25C, and increased the phosphorylation of CDC2 (Tyr15), an inactive form of CDC2. To examine the responsibilities of the p38 pathway for G(2) phase arrest induced by the TCTs, we employed the p38 inhibitor SB203580. SB203580 inhibited G(2) phase arrest, suppression of CDC25C, and phosphorylation of CDC2 (Tyr15) induced by the TCTs. These results suggest that the TCTs can induce G(2) phase arrest through activation of the p38 signaling pathway. We therefore believe that this combination is promising as a novel therapeutic strategy against ovarian cancer. Cognizant Communication Corporation 2017-09-21 /pmc/articles/PMC7841106/ /pubmed/28117030 http://dx.doi.org/10.3727/096504017X14850164661097 Text en Copyright © 2017 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License. |
spellingShingle | Article Akiyama, Makoto Sowa, Yoshihiro Taniguchi, Tomoyuki Watanabe, Motoki Yogosawa, Shingo Kitawaki, Jo Sakai, Toshiyuki Three Combined Treatments, a Novel HDAC Inhibitor OBP-801/YM753, 5-Fluorouracil, and Paclitaxel, Induce G(2) Phase Arrest Through the p38 Pathway in Human Ovarian Cancer Cells |
title | Three Combined Treatments, a Novel HDAC Inhibitor OBP-801/YM753, 5-Fluorouracil, and Paclitaxel, Induce G(2) Phase Arrest Through the p38 Pathway in Human Ovarian Cancer Cells |
title_full | Three Combined Treatments, a Novel HDAC Inhibitor OBP-801/YM753, 5-Fluorouracil, and Paclitaxel, Induce G(2) Phase Arrest Through the p38 Pathway in Human Ovarian Cancer Cells |
title_fullStr | Three Combined Treatments, a Novel HDAC Inhibitor OBP-801/YM753, 5-Fluorouracil, and Paclitaxel, Induce G(2) Phase Arrest Through the p38 Pathway in Human Ovarian Cancer Cells |
title_full_unstemmed | Three Combined Treatments, a Novel HDAC Inhibitor OBP-801/YM753, 5-Fluorouracil, and Paclitaxel, Induce G(2) Phase Arrest Through the p38 Pathway in Human Ovarian Cancer Cells |
title_short | Three Combined Treatments, a Novel HDAC Inhibitor OBP-801/YM753, 5-Fluorouracil, and Paclitaxel, Induce G(2) Phase Arrest Through the p38 Pathway in Human Ovarian Cancer Cells |
title_sort | three combined treatments, a novel hdac inhibitor obp-801/ym753, 5-fluorouracil, and paclitaxel, induce g(2) phase arrest through the p38 pathway in human ovarian cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841106/ https://www.ncbi.nlm.nih.gov/pubmed/28117030 http://dx.doi.org/10.3727/096504017X14850164661097 |
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