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Arginine depriving enzymes: applications as emerging therapeutics in cancer treatment

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Abstract

Cancer is the second leading cause of death globally. Chemotherapy and radiation therapy and other medications are employed to treat various types of cancer. However, each treatment has its own set of side effects, owing to its low specificity. As a result, there is an urgent need for newer therapeutics that do not disrupt healthy cells’ normal functioning. Depriving nutrient or non/semi-essential amino acids to which cancerous cells are auxotrophic remains one such promising anticancer strategy. l-Arginine (Arg) is a semi-essential vital amino acid involved in versatile metabolic processes, signaling pathways, and cancer cell proliferation. Hence, the administration of Arg depriving enzymes (ADE) such as arginase, arginine decarboxylase (ADC), and arginine deiminase (ADI) could be effective in cancer therapy. The Arg auxotrophic cancerous cells like hepatocellular carcinoma, human colon cancer, leukemia, and breast cancer cells are sensitive to ADE treatment due to low expression of crucial enzymes argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), and ornithine transcarbamylase (OCT). These therapeutic enzyme treatments induce cell death through inducing autophagy, apoptosis, generation of oxidative species, i.e., oxidative stress, and arresting the progression and expansion of cancerous cells at certain cell cycle checkpoints. The enzymes are undergoing clinical trials and could be successfully exploited as potential anticancer agents in the future.

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Abbreviations

Arg:

L-Arginine

ADE:

Arginine depriving enzymes

ADC:

Arginine decarboxylase

ADI:

Arginine deiminase

ASS:

Argininosuccinate synthetase

OCT:

Ornithine transcarbamylase

OAT:

Ornithine aminotransferase

ODC:

Ornithine decarboxylase

PEG:

Polyethylene glycol

hArg:

Human arginase

rhArg:

Recombinant human arginase

NO:

Nitric oxide

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Acknowledgements

The authors acknowledge Dr Ankit Shrivastava, LPVD, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT, 59840, USA, for his valuable suggestions during the drafting of the current study.

Funding

The authors acknowledge the Jaypee University of Information Technology Waknaghat, Solan, Himachal Pradesh, India, for providing infrastructure and financial support for carrying out the present work.

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  1. Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology Waknaghat, Solan, 173234, Himachal Pradesh, India

    Neha Kumari & Saurabh Bansal

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  1. Neha Kumari
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  2. Saurabh Bansal
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NK delineated, conducted the literature work, and wrote the manuscript. SB analyzes, reads, and approved the final submitted data.

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Correspondence to Saurabh Bansal.

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Kumari, N., Bansal, S. Arginine depriving enzymes: applications as emerging therapeutics in cancer treatment. Cancer Chemother Pharmacol 88, 565–594 (2021). https://doi.org/10.1007/s00280-021-04335-w

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