Sonlicromanol's active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth.

Aggressiveness of cancers, like prostate cancer, has been found to be associated with elevated expression of the microsomal prostaglandin E synthase-1 (mPGES-1). Here, we investigated whether KH176m (the active metabolite of sonlicromanol), a recently discovered selective mPGES-1 inhibitor, could af...

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Autores principales:	Xiaolan Jiang, Herma Renkema, Jan Smeitink, Julien Beyrath
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/66899fcd8dad41df877ed8c95e09000a
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spelling	oai:doaj.org-article:66899fcd8dad41df877ed8c95e09000a2021-12-02T20:09:18ZSonlicromanol's active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth.1932-620310.1371/journal.pone.0254315https://doaj.org/article/66899fcd8dad41df877ed8c95e09000a2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254315https://doaj.org/toc/1932-6203Aggressiveness of cancers, like prostate cancer, has been found to be associated with elevated expression of the microsomal prostaglandin E synthase-1 (mPGES-1). Here, we investigated whether KH176m (the active metabolite of sonlicromanol), a recently discovered selective mPGES-1 inhibitor, could affect prostate cancer cells-derived spheroid growth. We demonstrated that KH176m suppressed mPGES-1 expression and growth of DU145 (high mPGES-1 expression)-derived spheroids, while it had no effect on the LNCaP cell line, which has low mPGES-1 expression. By addition of exogenous PGE2, we found that the effect of KH176m on mPGES-1 expression and spheroid growth is due to the inhibition of a PGE2-driven positive feedback control-loop of mPGES-1 transcriptional regulation. Cancer stem cells (CSCs) are a subset of cancer cells exhibiting the ability of self-renewal, plasticity, and initiating and maintaining tumor growth. Our data shows that mPGES-1 is specifically expressed in this CSCs subpopulation (CD44+CD24-). KH176m inhibited the expression of mPGES-1 and reduced the growth of spheroids derived from the CSC. Based on the results obtained we propose selective mPGES-1 targeting by the sonlicromanol metabolite KH176m as a potential novel treatment approach for cancer patients with high mPGES-1 expression.Xiaolan JiangHerma RenkemaJan SmeitinkJulien BeyrathPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254315 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaolan Jiang Herma Renkema Jan Smeitink Julien Beyrath Sonlicromanol's active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth.
description	Aggressiveness of cancers, like prostate cancer, has been found to be associated with elevated expression of the microsomal prostaglandin E synthase-1 (mPGES-1). Here, we investigated whether KH176m (the active metabolite of sonlicromanol), a recently discovered selective mPGES-1 inhibitor, could affect prostate cancer cells-derived spheroid growth. We demonstrated that KH176m suppressed mPGES-1 expression and growth of DU145 (high mPGES-1 expression)-derived spheroids, while it had no effect on the LNCaP cell line, which has low mPGES-1 expression. By addition of exogenous PGE2, we found that the effect of KH176m on mPGES-1 expression and spheroid growth is due to the inhibition of a PGE2-driven positive feedback control-loop of mPGES-1 transcriptional regulation. Cancer stem cells (CSCs) are a subset of cancer cells exhibiting the ability of self-renewal, plasticity, and initiating and maintaining tumor growth. Our data shows that mPGES-1 is specifically expressed in this CSCs subpopulation (CD44+CD24-). KH176m inhibited the expression of mPGES-1 and reduced the growth of spheroids derived from the CSC. Based on the results obtained we propose selective mPGES-1 targeting by the sonlicromanol metabolite KH176m as a potential novel treatment approach for cancer patients with high mPGES-1 expression.
format	article
author	Xiaolan Jiang Herma Renkema Jan Smeitink Julien Beyrath
author_facet	Xiaolan Jiang Herma Renkema Jan Smeitink Julien Beyrath
author_sort	Xiaolan Jiang
title	Sonlicromanol's active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth.
title_short	Sonlicromanol's active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth.
title_full	Sonlicromanol's active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth.
title_fullStr	Sonlicromanol's active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth.
title_full_unstemmed	Sonlicromanol's active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth.
title_sort	sonlicromanol's active metabolite kh176m normalizes prostate cancer stem cell mpges-1 overexpression and inhibits cancer spheroid growth.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/66899fcd8dad41df877ed8c95e09000a
work_keys_str_mv	AT xiaolanjiang sonlicromanolsactivemetabolitekh176mnormalizesprostatecancerstemcellmpges1overexpressionandinhibitscancerspheroidgrowth AT hermarenkema sonlicromanolsactivemetabolitekh176mnormalizesprostatecancerstemcellmpges1overexpressionandinhibitscancerspheroidgrowth AT jansmeitink sonlicromanolsactivemetabolitekh176mnormalizesprostatecancerstemcellmpges1overexpressionandinhibitscancerspheroidgrowth AT julienbeyrath sonlicromanolsactivemetabolitekh176mnormalizesprostatecancerstemcellmpges1overexpressionandinhibitscancerspheroidgrowth
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Sonlicromanol's active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth.

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