Eribulin Mesylate Targets Human Telomerase Reverse Transcriptase in Ovarian Cancer Cells

Treatment of advanced ovarian cancer involves platinum-based chemotherapy. However, chemoresistance is a major obstacle. Cancer stem cells (CSCs) are thought to be one of the causes of chemoresistance, but the underlying mechanism remains elusive. Recently, human telomerase reverse transcriptase (hT...

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Main Authors:	Yamaguchi, Satoko, Maida, Yoshiko, Yasukawa, Mami, Kato, Tomoyasu, Yoshida, Masayuki, Masutomi, Kenkichi
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223061/

id	pubmed-4223061
recordtype	oai_dc
spelling	pubmed-42230612014-11-13 Eribulin Mesylate Targets Human Telomerase Reverse Transcriptase in Ovarian Cancer Cells Yamaguchi, Satoko Maida, Yoshiko Yasukawa, Mami Kato, Tomoyasu Yoshida, Masayuki Masutomi, Kenkichi Research Article Treatment of advanced ovarian cancer involves platinum-based chemotherapy. However, chemoresistance is a major obstacle. Cancer stem cells (CSCs) are thought to be one of the causes of chemoresistance, but the underlying mechanism remains elusive. Recently, human telomerase reverse transcriptase (hTERT) has been reported to promote CSC-like traits. In this study, we found that a mitotic inhibitor, eribulin mesylate (eribulin), effectively inhibited growth of platinum-resistant ovarian cancer cell lines. Eribulin-sensitive cells showed a higher efficiency for sphere formation, suggesting that these cells possess an enhanced CSC-like phenotype. Moreover, these cells expressed a higher level of hTERT, and suppression of hTERT expression by siRNA resulted in decreased sensitivity to eribulin, suggesting that hTERT may be a target for eribulin. Indeed, we found that eribulin directly inhibited RNA-dependent RNA polymerase (RdRP) activity, but not telomerase activity of hTERT in vitro. We propose that eribulin targets the RdRP activity of hTERT and may be an effective therapeutic option for CSCs. Furthermore, hTERT may be a useful biomarker to predict clinical responses to eribulin. Public Library of Science 2014-11-06 /pmc/articles/PMC4223061/ /pubmed/25375122 http://dx.doi.org/10.1371/journal.pone.0112438 Text en © 2014 Yamaguchi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yamaguchi, Satoko Maida, Yoshiko Yasukawa, Mami Kato, Tomoyasu Yoshida, Masayuki Masutomi, Kenkichi
spellingShingle	Yamaguchi, Satoko Maida, Yoshiko Yasukawa, Mami Kato, Tomoyasu Yoshida, Masayuki Masutomi, Kenkichi Eribulin Mesylate Targets Human Telomerase Reverse Transcriptase in Ovarian Cancer Cells
author_facet	Yamaguchi, Satoko Maida, Yoshiko Yasukawa, Mami Kato, Tomoyasu Yoshida, Masayuki Masutomi, Kenkichi
author_sort	Yamaguchi, Satoko
title	Eribulin Mesylate Targets Human Telomerase Reverse Transcriptase in Ovarian Cancer Cells
title_short	Eribulin Mesylate Targets Human Telomerase Reverse Transcriptase in Ovarian Cancer Cells
title_full	Eribulin Mesylate Targets Human Telomerase Reverse Transcriptase in Ovarian Cancer Cells
title_fullStr	Eribulin Mesylate Targets Human Telomerase Reverse Transcriptase in Ovarian Cancer Cells
title_full_unstemmed	Eribulin Mesylate Targets Human Telomerase Reverse Transcriptase in Ovarian Cancer Cells
title_sort	eribulin mesylate targets human telomerase reverse transcriptase in ovarian cancer cells
description	Treatment of advanced ovarian cancer involves platinum-based chemotherapy. However, chemoresistance is a major obstacle. Cancer stem cells (CSCs) are thought to be one of the causes of chemoresistance, but the underlying mechanism remains elusive. Recently, human telomerase reverse transcriptase (hTERT) has been reported to promote CSC-like traits. In this study, we found that a mitotic inhibitor, eribulin mesylate (eribulin), effectively inhibited growth of platinum-resistant ovarian cancer cell lines. Eribulin-sensitive cells showed a higher efficiency for sphere formation, suggesting that these cells possess an enhanced CSC-like phenotype. Moreover, these cells expressed a higher level of hTERT, and suppression of hTERT expression by siRNA resulted in decreased sensitivity to eribulin, suggesting that hTERT may be a target for eribulin. Indeed, we found that eribulin directly inhibited RNA-dependent RNA polymerase (RdRP) activity, but not telomerase activity of hTERT in vitro. We propose that eribulin targets the RdRP activity of hTERT and may be an effective therapeutic option for CSCs. Furthermore, hTERT may be a useful biomarker to predict clinical responses to eribulin.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223061/
_version_	1613153341874896896

Eribulin Mesylate Targets Human Telomerase Reverse Transcriptase in Ovarian Cancer Cells

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