All-trans retinoic acid and protein kinase C α/β1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression

Abstract Breast cancer is the leading cause of cancer death among women worldwide. Blocking a single signaling pathway is often an ineffective therapy, especially in the case of aggressive or drug-resistant tumors. Since we have previously described the mechanism involved in the crosstalk between Re...

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Autores principales:	Damian Emilio Berardi, Lizeth Ariza Bareño, Natalia Amigo, Luciana Cañonero, Maria de las Nieves Pelagatti, Andrea Nora Motter, María Agustina Taruselli, María Inés Díaz Bessone, Stefano Martin Cirigliano, Alexis Edelstein, María Giselle Peters, Miriam Diament, Alejandro Jorge Urtreger, Laura Beatriz Todaro
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/01e93465ea7b4915836df1684987bcd4
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spelling	oai:doaj.org-article:01e93465ea7b4915836df1684987bcd42021-12-02T11:39:43ZAll-trans retinoic acid and protein kinase C α/β1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression10.1038/s41598-021-85344-w2045-2322https://doaj.org/article/01e93465ea7b4915836df1684987bcd42021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85344-whttps://doaj.org/toc/2045-2322Abstract Breast cancer is the leading cause of cancer death among women worldwide. Blocking a single signaling pathway is often an ineffective therapy, especially in the case of aggressive or drug-resistant tumors. Since we have previously described the mechanism involved in the crosstalk between Retinoic Acid system and protein kinase C (PKC) pathway, the rationale of our study was to evaluate the effect of combining all-trans-retinoic acid (ATRA) with a classical PCK inhibitor (Gö6976) in preclinical settings. Employing hormone-independent mammary cancer models, Gö6976 and ATRA combined treatment induced a synergistic reduction in proliferative potential that correlated with an increased apoptosis and RARs modulation towards an anti-oncogenic profile. Combined treatment also impairs growth, self-renewal and clonogenicity potential of cancer stem cells and reduced tumor growth, metastatic spread and cancer stem cells frequency in vivo. An in-silico analysis of “Kaplan–Meier plotter” database indicated that low PKCα together with high RARα mRNA expression is a favorable prognosis factor for hormone-independent breast cancer patients. Here we demonstrate that a classical PKC inhibitor potentiates ATRA antitumor effects also targeting cancer stem cells growth, self-renewal and frequency.Damian Emilio BerardiLizeth Ariza BareñoNatalia AmigoLuciana CañoneroMaria de las Nieves PelagattiAndrea Nora MotterMaría Agustina TaruselliMaría Inés Díaz BessoneStefano Martin CiriglianoAlexis EdelsteinMaría Giselle PetersMiriam DiamentAlejandro Jorge UrtregerLaura Beatriz TodaroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Damian Emilio Berardi Lizeth Ariza Bareño Natalia Amigo Luciana Cañonero Maria de las Nieves Pelagatti Andrea Nora Motter María Agustina Taruselli María Inés Díaz Bessone Stefano Martin Cirigliano Alexis Edelstein María Giselle Peters Miriam Diament Alejandro Jorge Urtreger Laura Beatriz Todaro All-trans retinoic acid and protein kinase C α/β1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression
description	Abstract Breast cancer is the leading cause of cancer death among women worldwide. Blocking a single signaling pathway is often an ineffective therapy, especially in the case of aggressive or drug-resistant tumors. Since we have previously described the mechanism involved in the crosstalk between Retinoic Acid system and protein kinase C (PKC) pathway, the rationale of our study was to evaluate the effect of combining all-trans-retinoic acid (ATRA) with a classical PCK inhibitor (Gö6976) in preclinical settings. Employing hormone-independent mammary cancer models, Gö6976 and ATRA combined treatment induced a synergistic reduction in proliferative potential that correlated with an increased apoptosis and RARs modulation towards an anti-oncogenic profile. Combined treatment also impairs growth, self-renewal and clonogenicity potential of cancer stem cells and reduced tumor growth, metastatic spread and cancer stem cells frequency in vivo. An in-silico analysis of “Kaplan–Meier plotter” database indicated that low PKCα together with high RARα mRNA expression is a favorable prognosis factor for hormone-independent breast cancer patients. Here we demonstrate that a classical PKC inhibitor potentiates ATRA antitumor effects also targeting cancer stem cells growth, self-renewal and frequency.
format	article
author	Damian Emilio Berardi Lizeth Ariza Bareño Natalia Amigo Luciana Cañonero Maria de las Nieves Pelagatti Andrea Nora Motter María Agustina Taruselli María Inés Díaz Bessone Stefano Martin Cirigliano Alexis Edelstein María Giselle Peters Miriam Diament Alejandro Jorge Urtreger Laura Beatriz Todaro
author_facet	Damian Emilio Berardi Lizeth Ariza Bareño Natalia Amigo Luciana Cañonero Maria de las Nieves Pelagatti Andrea Nora Motter María Agustina Taruselli María Inés Díaz Bessone Stefano Martin Cirigliano Alexis Edelstein María Giselle Peters Miriam Diament Alejandro Jorge Urtreger Laura Beatriz Todaro
author_sort	Damian Emilio Berardi
title	All-trans retinoic acid and protein kinase C α/β1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression
title_short	All-trans retinoic acid and protein kinase C α/β1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression
title_full	All-trans retinoic acid and protein kinase C α/β1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression
title_fullStr	All-trans retinoic acid and protein kinase C α/β1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression
title_full_unstemmed	All-trans retinoic acid and protein kinase C α/β1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression
title_sort	all-trans retinoic acid and protein kinase c α/β1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/01e93465ea7b4915836df1684987bcd4
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All-trans retinoic acid and protein kinase C α/β1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression

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