Concomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-β-treated epithelial cancer cells

Abstract Epithelial-mesenchymal transition (EMT) in primary tumor cells is a key prerequisite for metastasis initiation. Statins, cholesterol-lowering drugs, can delay metastasis formation in vivo and attenuate the growth and proliferation of tumor cells in vitro. The latter effect is stronger in tu...

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Autores principales:	Katsuhiko Warita, Takuro Ishikawa, Akihiro Sugiura, Jiro Tashiro, Hiroaki Shimakura, Yoshinao Z. Hosaka, Ken-ichi Ohta, Tomoko Warita, Zoltán N. Oltvai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a650d544c42a44f6a90b04ef570211af
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spelling	oai:doaj.org-article:a650d544c42a44f6a90b04ef570211af2021-12-02T17:41:29ZConcomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-β-treated epithelial cancer cells10.1038/s41598-021-91928-32045-2322https://doaj.org/article/a650d544c42a44f6a90b04ef570211af2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91928-3https://doaj.org/toc/2045-2322Abstract Epithelial-mesenchymal transition (EMT) in primary tumor cells is a key prerequisite for metastasis initiation. Statins, cholesterol-lowering drugs, can delay metastasis formation in vivo and attenuate the growth and proliferation of tumor cells in vitro. The latter effect is stronger in tumor cells with a mesenchymal-like phenotype than in those with an epithelial one. However, the effect of statins on epithelial cancer cells treated with EMT-inducing growth factors such as transforming growth factor-β (TGF-β) remains unclear. Here, we examined the effect of atorvastatin on two epithelial cancer cell lines following TGF-β treatment. Atorvastatin-induced growth inhibition was stronger in TGF-β-treated cells than in cells not thusly treated. Moreover, treatment of cells with atorvastatin prior to TGF-β treatment enhanced this effect, which was further potentiated by the simultaneous reduction in the expression of the statin target enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Dual pharmacological targeting of HMGCR can thus strongly inhibit the growth and proliferation of epithelial cancer cells treated with TGF-β and may also improve statin therapy-mediated attenuation of metastasis formation in vivo.Katsuhiko WaritaTakuro IshikawaAkihiro SugiuraJiro TashiroHiroaki ShimakuraYoshinao Z. HosakaKen-ichi OhtaTomoko WaritaZoltán N. OltvaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katsuhiko Warita Takuro Ishikawa Akihiro Sugiura Jiro Tashiro Hiroaki Shimakura Yoshinao Z. Hosaka Ken-ichi Ohta Tomoko Warita Zoltán N. Oltvai Concomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-β-treated epithelial cancer cells
description	Abstract Epithelial-mesenchymal transition (EMT) in primary tumor cells is a key prerequisite for metastasis initiation. Statins, cholesterol-lowering drugs, can delay metastasis formation in vivo and attenuate the growth and proliferation of tumor cells in vitro. The latter effect is stronger in tumor cells with a mesenchymal-like phenotype than in those with an epithelial one. However, the effect of statins on epithelial cancer cells treated with EMT-inducing growth factors such as transforming growth factor-β (TGF-β) remains unclear. Here, we examined the effect of atorvastatin on two epithelial cancer cell lines following TGF-β treatment. Atorvastatin-induced growth inhibition was stronger in TGF-β-treated cells than in cells not thusly treated. Moreover, treatment of cells with atorvastatin prior to TGF-β treatment enhanced this effect, which was further potentiated by the simultaneous reduction in the expression of the statin target enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Dual pharmacological targeting of HMGCR can thus strongly inhibit the growth and proliferation of epithelial cancer cells treated with TGF-β and may also improve statin therapy-mediated attenuation of metastasis formation in vivo.
format	article
author	Katsuhiko Warita Takuro Ishikawa Akihiro Sugiura Jiro Tashiro Hiroaki Shimakura Yoshinao Z. Hosaka Ken-ichi Ohta Tomoko Warita Zoltán N. Oltvai
author_facet	Katsuhiko Warita Takuro Ishikawa Akihiro Sugiura Jiro Tashiro Hiroaki Shimakura Yoshinao Z. Hosaka Ken-ichi Ohta Tomoko Warita Zoltán N. Oltvai
author_sort	Katsuhiko Warita
title	Concomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-β-treated epithelial cancer cells
title_short	Concomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-β-treated epithelial cancer cells
title_full	Concomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-β-treated epithelial cancer cells
title_fullStr	Concomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-β-treated epithelial cancer cells
title_full_unstemmed	Concomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-β-treated epithelial cancer cells
title_sort	concomitant attenuation of hmgcr expression and activity enhances the growth inhibitory effect of atorvastatin on tgf-β-treated epithelial cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a650d544c42a44f6a90b04ef570211af
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Concomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-β-treated epithelial cancer cells

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