Arginase-induced cell death pathways and metabolic changes in cancer cells are not altered by insulin
Abstract Arginine, a semi-essential amino acid, is critical for cell growth. Typically, de novo synthesis of arginine is sufficient to support cellular processes, however, it becomes vital for cancer cells that are unable to synthesise arginine due to enzyme deficiencies. Targeting this need, argini...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-54520-z |
| _version_ | 1797274796644368384 |
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| author | Hui Yi Chew Goran Cvetkovic Slobodan Tepic James W. Wells |
| author_facet | Hui Yi Chew Goran Cvetkovic Slobodan Tepic James W. Wells |
| author_sort | Hui Yi Chew |
| collection | DOAJ |
| description | Abstract Arginine, a semi-essential amino acid, is critical for cell growth. Typically, de novo synthesis of arginine is sufficient to support cellular processes, however, it becomes vital for cancer cells that are unable to synthesise arginine due to enzyme deficiencies. Targeting this need, arginine depletion with enzymes such as arginase (ARG) has emerged as a potential cancer therapeutic strategy. Studies have proposed using high dose insulin to induce a state of hypoaminoacidaemia in the body, thereby further reducing circulating arginine levels. However, the mitogenic and metabolic properties of insulin could potentially counteract the therapeutic effects of ARG. Our study examined the combined impact of insulin and ARG on breast, lung, and ovarian cell lines, focusing on cell proliferation, metabolism, apoptosis, and autophagy. Our results showed that the influence of insulin on ARG uptake varied between cell lines but failed to promote the proliferation of ARG-treated cells or aid recovery post-ARG treatment. Moreover, insulin was largely ineffective in altering ARG-induced metabolic changes and did not prevent apoptosis. In vitro, at least, these findings imply that insulin does not offer a growth or survival benefit to cancer cells being treated with ARG. |
| first_indexed | 2024-03-07T15:04:04Z |
| format | Article |
| id | doaj.art-3027cf5bec4d42bf89f2c65de2bdf696 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:04:04Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3027cf5bec4d42bf89f2c65de2bdf6962024-03-05T18:59:24ZengNature PortfolioScientific Reports2045-23222024-02-0114111210.1038/s41598-024-54520-zArginase-induced cell death pathways and metabolic changes in cancer cells are not altered by insulinHui Yi Chew0Goran Cvetkovic1Slobodan Tepic2James W. Wells3Faculty of Medicine, Frazer Institute, The University of QueenslandHepius Biotech AGHepius Biotech AGFaculty of Medicine, Frazer Institute, The University of QueenslandAbstract Arginine, a semi-essential amino acid, is critical for cell growth. Typically, de novo synthesis of arginine is sufficient to support cellular processes, however, it becomes vital for cancer cells that are unable to synthesise arginine due to enzyme deficiencies. Targeting this need, arginine depletion with enzymes such as arginase (ARG) has emerged as a potential cancer therapeutic strategy. Studies have proposed using high dose insulin to induce a state of hypoaminoacidaemia in the body, thereby further reducing circulating arginine levels. However, the mitogenic and metabolic properties of insulin could potentially counteract the therapeutic effects of ARG. Our study examined the combined impact of insulin and ARG on breast, lung, and ovarian cell lines, focusing on cell proliferation, metabolism, apoptosis, and autophagy. Our results showed that the influence of insulin on ARG uptake varied between cell lines but failed to promote the proliferation of ARG-treated cells or aid recovery post-ARG treatment. Moreover, insulin was largely ineffective in altering ARG-induced metabolic changes and did not prevent apoptosis. In vitro, at least, these findings imply that insulin does not offer a growth or survival benefit to cancer cells being treated with ARG.https://doi.org/10.1038/s41598-024-54520-z |
| spellingShingle | Hui Yi Chew Goran Cvetkovic Slobodan Tepic James W. Wells Arginase-induced cell death pathways and metabolic changes in cancer cells are not altered by insulin Scientific Reports |
| title | Arginase-induced cell death pathways and metabolic changes in cancer cells are not altered by insulin |
| title_full | Arginase-induced cell death pathways and metabolic changes in cancer cells are not altered by insulin |
| title_fullStr | Arginase-induced cell death pathways and metabolic changes in cancer cells are not altered by insulin |
| title_full_unstemmed | Arginase-induced cell death pathways and metabolic changes in cancer cells are not altered by insulin |
| title_short | Arginase-induced cell death pathways and metabolic changes in cancer cells are not altered by insulin |
| title_sort | arginase induced cell death pathways and metabolic changes in cancer cells are not altered by insulin |
| url | https://doi.org/10.1038/s41598-024-54520-z |
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