Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells

Abstract Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezom...

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Autores principales:	Monica Benvenuto, Sara Ciuffa, Chiara Focaccetti, Diego Sbardella, Sara Fazi, Manuel Scimeca, Grazia Raffaella Tundo, Giovanni Barillari, Maria Segni, Elena Bonanno, Vittorio Manzari, Andrea Modesti, Laura Masuelli, Massimo Coletta, Roberto Bei
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fb341c343f084ed79de8be99b14fac49
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spelling	oai:doaj.org-article:fb341c343f084ed79de8be99b14fac492021-12-02T18:14:30ZProteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells10.1038/s41598-021-98450-62045-2322https://doaj.org/article/fb341c343f084ed79de8be99b14fac492021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98450-6https://doaj.org/toc/2045-2322Abstract Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human tongue (SCC-15, CAL-27), pharynx (FaDu), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) originated from a salivary gland adenocarcinoma arising in BALB-neuT male mice transgenic for the oncogene neu. Bortezomib inhibited cell proliferation, triggered apoptosis, modulated the expression and activation of pro-survival signaling transduction pathways proteins activated by ErbB receptors and inhibited proteasome activity in vitro. Intraperitoneal administration of Bortezomib delayed tumor growth of SALTO-5 cells transplanted in BALB-neuT mice, protracted mice survival and adjusted tumor microenvironment by increasing tumor-infiltrating immune cells (CD4+ and CD8+ T cells, B lymphocytes, macrophages, and Natural Killer cells) and by decreasing vessels density. In addition, Bortezomib modified the expression of proteasome structural subunits in transplanted SALTO-5 cells. Our findings further support the use of Bortezomib for the treatment of HNC and reveal its ineffectiveness in counteracting the activation of deregulated specific signaling pathways in HNC cell lines when resistance to proteasome inhibition is developed.Monica BenvenutoSara CiuffaChiara FocaccettiDiego SbardellaSara FaziManuel ScimecaGrazia Raffaella TundoGiovanni BarillariMaria SegniElena BonannoVittorio ManzariAndrea ModestiLaura MasuelliMassimo ColettaRoberto BeiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-23 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Monica Benvenuto Sara Ciuffa Chiara Focaccetti Diego Sbardella Sara Fazi Manuel Scimeca Grazia Raffaella Tundo Giovanni Barillari Maria Segni Elena Bonanno Vittorio Manzari Andrea Modesti Laura Masuelli Massimo Coletta Roberto Bei Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells
description	Abstract Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human tongue (SCC-15, CAL-27), pharynx (FaDu), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) originated from a salivary gland adenocarcinoma arising in BALB-neuT male mice transgenic for the oncogene neu. Bortezomib inhibited cell proliferation, triggered apoptosis, modulated the expression and activation of pro-survival signaling transduction pathways proteins activated by ErbB receptors and inhibited proteasome activity in vitro. Intraperitoneal administration of Bortezomib delayed tumor growth of SALTO-5 cells transplanted in BALB-neuT mice, protracted mice survival and adjusted tumor microenvironment by increasing tumor-infiltrating immune cells (CD4+ and CD8+ T cells, B lymphocytes, macrophages, and Natural Killer cells) and by decreasing vessels density. In addition, Bortezomib modified the expression of proteasome structural subunits in transplanted SALTO-5 cells. Our findings further support the use of Bortezomib for the treatment of HNC and reveal its ineffectiveness in counteracting the activation of deregulated specific signaling pathways in HNC cell lines when resistance to proteasome inhibition is developed.
format	article
author	Monica Benvenuto Sara Ciuffa Chiara Focaccetti Diego Sbardella Sara Fazi Manuel Scimeca Grazia Raffaella Tundo Giovanni Barillari Maria Segni Elena Bonanno Vittorio Manzari Andrea Modesti Laura Masuelli Massimo Coletta Roberto Bei
author_facet	Monica Benvenuto Sara Ciuffa Chiara Focaccetti Diego Sbardella Sara Fazi Manuel Scimeca Grazia Raffaella Tundo Giovanni Barillari Maria Segni Elena Bonanno Vittorio Manzari Andrea Modesti Laura Masuelli Massimo Coletta Roberto Bei
author_sort	Monica Benvenuto
title	Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells
title_short	Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells
title_full	Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells
title_fullStr	Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells
title_full_unstemmed	Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells
title_sort	proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fb341c343f084ed79de8be99b14fac49
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Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells

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