Glutaminase - A potential target for cancer treatment

Josephine Anthony, Department of Research, Meenakshi Academy of Higher Education and Research (MAHER- 7 Deemed to be University), Chennai 600 078, Tamil Nadu, IndiaFollow
Sureka Varalakshmi, Department of Research, Meenakshi Academy of Higher Education and Research (MAHER- 7 Deemed to be University), Chennai 600 078, Tamil Nadu, India
Ashok Kumar Sekar, Centre for Biotechnology, Anna University, Chennai-600 025, Tamil Nadu, India
Nalini Devarajan, Department of Research, Meenakshi Academy of Higher Education and Research (MAHER- 7 Deemed to be University), Chennai 600 078, Tamil Nadu, India
Balamurugan Janakiraman, SRM College of Physiotherapy, Faculty of Medicine and Health Sciences, SRM Institute of 10 Science and Technology (SRMIST), Kattankulathur, Tamil Nadu 603203, India
Rajendran Peramaiyan, Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa, 12 31982, Kingdom of Saudi Arabia

Abstract

The overexpression of glutaminase is reported to influence cancer growth and metastasis through glutaminolysis. Upregulation of glutamine catabolism is recently recognized as a critical feature of cancer, and cancer cells are observed to reprogram glutamine metabolism to maintain its survival and proliferation. Special focus is given on the glutaminase isoform, GLS1 (kidney type glutaminase), as the other isoform GLS2 (Liver type glutaminase) acts as a tumour suppressor in some conditions. Glutaminolysis linked with autophagy, which is mediated via mTORC1, also serves as a promising target for cancer therapy. Glutamine also plays a vital role in maintaining redox homeostasis. Inhibition of glutaminase aggravates oxidative stress by reducing glutathione level, thus leading to apoptotic-mediated cell death in cancer cells Therefore, inhibiting the glutaminase activity using glutaminase inhibitors such as BPTES, DON, JHU-083, CB-839, compound 968, etc. may answer many intriguing questions behind the uncontrolled proliferation of cancer cells and serve as a prophylactic treatment for cancer. Earlier reports neither discuss nor provide perspectives on exact signaling gene or pathway. Hence, the present review highlights the plausible role of glutaminase in cancer and the current therapeutic approaches and clinical trials to target and inhibit glutaminase enzymes for better cancer treatment.

Recommended Citation

Anthony, Josephine; Varalakshmi, Sureka; Sekar, Ashok Kumar; Devarajan, Nalini; Janakiraman, Balamurugan; and Peramaiyan, Rajendran (2024) "Glutaminase - A potential target for cancer treatment," BioMedicine: Vol. 14 : Iss. 2 , Article 3.
DOI: 10.37796/2211-8039.1445