Targeting cellular metabolism to reduce head and neck cancer growth

Abstract Head and neck squamous cell carcinoma (HNSCC) presents a major public health concern because of delayed diagnosis and poor prognosis. Malignant cells often reprogram their metabolism in order to promote their survival and proliferation. Aberrant glutaminase 1 (GLS1) expression enables malig...

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Autores principales:	Jian Yang, Yuqi Guo, Wonkyu Seo, Ruohan Zhang, Cuijie Lu, Yaoyu Wang, Liang Luo, Bidisha Paul, Wenbo Yan, Deepak Saxena, Xin Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/632e3ccde758438fb07bb3375184341a
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spelling	oai:doaj.org-article:632e3ccde758438fb07bb3375184341a2021-12-02T16:08:28ZTargeting cellular metabolism to reduce head and neck cancer growth10.1038/s41598-019-41523-42045-2322https://doaj.org/article/632e3ccde758438fb07bb3375184341a2019-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-41523-4https://doaj.org/toc/2045-2322Abstract Head and neck squamous cell carcinoma (HNSCC) presents a major public health concern because of delayed diagnosis and poor prognosis. Malignant cells often reprogram their metabolism in order to promote their survival and proliferation. Aberrant glutaminase 1 (GLS1) expression enables malignant cells to undergo increased glutaminolysis and utilization of glutamine as an alternative nutrient. In this study, we found a significantly elevated GLS1 expression in HNSCC, and patients with high expression levels of GLS1 experienced shorter disease-free periods after therapy. We hypothesized that the GLS1 selective inhibitor, bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES), which curtails cells’ glutamine consumption, may inhibit HNSCC cell growth. Our results support the idea that BPTES inhibits HNSCC growth by inducing apoptosis and cell cycle arrest. Considering that metformin can reduce glucose consumption, we speculated that metformin would enhance the anti-neoplasia effect of BPTES by suppressing malignant cells’ glucose utilization. The combination of both compounds exhibited an additive inhibitory effect on cancer cell survival and proliferation. All of our data suggest that GLS1 is a promising therapeutic target for HNSCC treatment. Combining BPTES with metformin might achieve improved anti-cancer effects in HNSSC, which sheds light on using novel therapeutic strategies by dually targeting cellular metabolism.Jian YangYuqi GuoWonkyu SeoRuohan ZhangCuijie LuYaoyu WangLiang LuoBidisha PaulWenbo YanDeepak SaxenaXin LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jian Yang Yuqi Guo Wonkyu Seo Ruohan Zhang Cuijie Lu Yaoyu Wang Liang Luo Bidisha Paul Wenbo Yan Deepak Saxena Xin Li Targeting cellular metabolism to reduce head and neck cancer growth
description	Abstract Head and neck squamous cell carcinoma (HNSCC) presents a major public health concern because of delayed diagnosis and poor prognosis. Malignant cells often reprogram their metabolism in order to promote their survival and proliferation. Aberrant glutaminase 1 (GLS1) expression enables malignant cells to undergo increased glutaminolysis and utilization of glutamine as an alternative nutrient. In this study, we found a significantly elevated GLS1 expression in HNSCC, and patients with high expression levels of GLS1 experienced shorter disease-free periods after therapy. We hypothesized that the GLS1 selective inhibitor, bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES), which curtails cells’ glutamine consumption, may inhibit HNSCC cell growth. Our results support the idea that BPTES inhibits HNSCC growth by inducing apoptosis and cell cycle arrest. Considering that metformin can reduce glucose consumption, we speculated that metformin would enhance the anti-neoplasia effect of BPTES by suppressing malignant cells’ glucose utilization. The combination of both compounds exhibited an additive inhibitory effect on cancer cell survival and proliferation. All of our data suggest that GLS1 is a promising therapeutic target for HNSCC treatment. Combining BPTES with metformin might achieve improved anti-cancer effects in HNSSC, which sheds light on using novel therapeutic strategies by dually targeting cellular metabolism.
format	article
author	Jian Yang Yuqi Guo Wonkyu Seo Ruohan Zhang Cuijie Lu Yaoyu Wang Liang Luo Bidisha Paul Wenbo Yan Deepak Saxena Xin Li
author_facet	Jian Yang Yuqi Guo Wonkyu Seo Ruohan Zhang Cuijie Lu Yaoyu Wang Liang Luo Bidisha Paul Wenbo Yan Deepak Saxena Xin Li
author_sort	Jian Yang
title	Targeting cellular metabolism to reduce head and neck cancer growth
title_short	Targeting cellular metabolism to reduce head and neck cancer growth
title_full	Targeting cellular metabolism to reduce head and neck cancer growth
title_fullStr	Targeting cellular metabolism to reduce head and neck cancer growth
title_full_unstemmed	Targeting cellular metabolism to reduce head and neck cancer growth
title_sort	targeting cellular metabolism to reduce head and neck cancer growth
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/632e3ccde758438fb07bb3375184341a
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Targeting cellular metabolism to reduce head and neck cancer growth

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