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Review
. 2024 Jun 1;14(2):29-37.
doi: 10.37796/2211-8039.1445. eCollection 2024.

Glutaminase - A potential target for cancer treatment

Josephine Anthony  1 , Sureka Varalakshmi  1 , Ashok Kumar Sekar  2 , Nalini Devarajan  1 , Balamurugan Janakiraman  3 , Rajendran Peramaiyan  4   5
Affiliations
Review

Glutaminase - A potential target for cancer treatment

Josephine Anthony et al. Biomedicine (Taipei). .

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.

Keywords: Autophagy; Cancer; Glutaminase; Glutaminase inhibitor; Glutamine; Redox homeostasis.

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Conflict of interest statement

Conflicts of interest: All the authors declare that there is no conflict of interest in the content of this article.

Figures

Fig. 1
Fig. 1
A schematic illustration representing the association between glutaminase, mTOR and autophagy in cancer.
See this image and copyright information in PMC

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Grants and funding

The first author (JA) received seed money research support fund (Ref: MAHER/Research/SMG/2023-050) from Meenakshi Academy of Higher Education and Research (MAHER), Chennai, India

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