Remarkable Effect of Increasing Glutamine Metabolism on Caveolin-1 in Breast Cancer: A Brief Report

Author:

Mostafavi Samaneh1,Hadjati Jamshid2,Mostafazadeh Amrollah3,Hassan Zuhair Mohammad1

Affiliation:

1. Tarbiat Modares University

2. Tehran University of Medical Sciences

3. Babol University of Medical Sciences

Abstract

Abstract Background Caveolin-1(CAV-1) is a key molecule in cancer metabolism and progression and decrease in highly metastatic breast cancer cells. Moreover, glutamine is a crucial amino acid in the tumor microenvironment, and cancer cells are addicted to it. The effect of glutamine metabolism on caveoline-1 was not completely clarified. However, metformin has been demonstrated in separate studies to impair glutamine metabolism, and also affect caveoline-1 expression. Hence, the focus of this study is to evaluate the effect of glutamine metabolism on caveoline-1 expression, and to examine if metformin could affect caveoline-1 in high glutamine media. Methods In this study, 4T1 breast cancer cell line was cultured in different concentrations of glutamine. Caveolin-1 expression was assessed, using immunocytochemistry test. We also conducted MTT assay to evaluate optimum dose for metformin. To understand if metformin could regulate caveoline-1 expression in high glutamine media, 5mM of metformin was administrated and compared with control. Results our results indicated that glutamine metabolism significantly decreased CAV-1. On the other hand, administration of 5mM metformin for 24 hours efficiently re-expressed CAV-1. Conclusion High level of glutamine significantly decreased CAV-1, which may up-regulate the possibility of breast tumor speared, metastasis and metabolic reprogramming. Metformin, however, could be a promising drug, targeting glutamine metabolism to re-express caveoline-1, inhibiting tumor progression and metastasis.

Publisher

Research Square Platform LLC

Reference21 articles.

1. Li T, Copeland C, Le A. Glutamine Metabolism in Cancer. In: Le A, editor. The Heterogeneity of Cancer Metabolism. Cham: Springer International Publishing; 2021. p. 17–38.

2. Eagle H. The minimum vitamin requirements of the L and HeLa cells in tissue culture, the production of specific vitamin deficiencies, and their cure. The Journal of experimental medicine. 1955 Nov 1;102(5):595–600. Epub 1955/11/01. eng.

3. Enhancing the Efficacy of Glutamine Metabolism Inhibitors in Cancer Therapy;Yang WH QY;Trends Cancer,2021

4. The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors;Mostafavi S;Cellular & molecular biology letters,2022

5. Bost F, Rena G, Viollet B. Editorial: Metformin: Beyond Diabetes. Frontiers in endocrinology. 2019;10:851. eng.

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