Methylmalonic acid at the serum level in the elderly contributes to cell growth via mitochondrial dysfunction in colorectal cancer cell spheroids

Methylmalonic acid (MMA) is a small molecule produced during the metabolism of propionate and branched-chain amino acids. Recently, it has been reported that the blood concentration of MMA increases with age and promotes lung cancer metastasis. However, little is known regarding its effects on cance...

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Main Authors: Arowu R. Tanaka, Chiho Murakami, Hideya Yamamoto
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Biochemistry and Biophysics Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405580824002735
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author Arowu R. Tanaka
Chiho Murakami
Hideya Yamamoto
author_facet Arowu R. Tanaka
Chiho Murakami
Hideya Yamamoto
author_sort Arowu R. Tanaka
collection DOAJ
description Methylmalonic acid (MMA) is a small molecule produced during the metabolism of propionate and branched-chain amino acids. Recently, it has been reported that the blood concentration of MMA increases with age and promotes lung cancer metastasis. However, little is known regarding its effects on cancers other than lung cancer. In the present study, we examined the effects of MMA on colorectal cancer cell spheroids. We found that MMA promoted the proliferation of colorectal cancer spheroids at physiological concentrations that can be exhibited by the elderly and induced mitochondrial reactive oxygen species generation, which in turn affected the promotion of cell growth. MMA treatment also induces a metabolic shift in the glycolytic system. These results suggest that MMA may promote cancer cell proliferation by decreasing mitochondrial function, inducing a metabolic shift, and provide new insights into the effects of aging on cancer.
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issn 2405-5808
language English
publishDate 2025-03-01
publisher Elsevier
record_format Article
series Biochemistry and Biophysics Reports
spelling doaj-art-cca415f22d174ab0bb4f02446d898dc92025-08-20T02:47:10ZengElsevierBiochemistry and Biophysics Reports2405-58082025-03-014110190910.1016/j.bbrep.2024.101909Methylmalonic acid at the serum level in the elderly contributes to cell growth via mitochondrial dysfunction in colorectal cancer cell spheroidsArowu R. Tanaka0Chiho Murakami1Hideya Yamamoto2Corresponding author.; Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami Ward, Hiroshima City, Hiroshima, 731-0153, JapanFaculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami Ward, Hiroshima City, Hiroshima, 731-0153, JapanFaculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami Ward, Hiroshima City, Hiroshima, 731-0153, JapanMethylmalonic acid (MMA) is a small molecule produced during the metabolism of propionate and branched-chain amino acids. Recently, it has been reported that the blood concentration of MMA increases with age and promotes lung cancer metastasis. However, little is known regarding its effects on cancers other than lung cancer. In the present study, we examined the effects of MMA on colorectal cancer cell spheroids. We found that MMA promoted the proliferation of colorectal cancer spheroids at physiological concentrations that can be exhibited by the elderly and induced mitochondrial reactive oxygen species generation, which in turn affected the promotion of cell growth. MMA treatment also induces a metabolic shift in the glycolytic system. These results suggest that MMA may promote cancer cell proliferation by decreasing mitochondrial function, inducing a metabolic shift, and provide new insights into the effects of aging on cancer.http://www.sciencedirect.com/science/article/pii/S2405580824002735AgingCancerGlutamineMitochondriaGlycolytic systemMethylmalonic acid
spellingShingle Arowu R. Tanaka
Chiho Murakami
Hideya Yamamoto
Methylmalonic acid at the serum level in the elderly contributes to cell growth via mitochondrial dysfunction in colorectal cancer cell spheroids
Biochemistry and Biophysics Reports
Aging
Cancer
Glutamine
Mitochondria
Glycolytic system
Methylmalonic acid
title Methylmalonic acid at the serum level in the elderly contributes to cell growth via mitochondrial dysfunction in colorectal cancer cell spheroids
title_full Methylmalonic acid at the serum level in the elderly contributes to cell growth via mitochondrial dysfunction in colorectal cancer cell spheroids
title_fullStr Methylmalonic acid at the serum level in the elderly contributes to cell growth via mitochondrial dysfunction in colorectal cancer cell spheroids
title_full_unstemmed Methylmalonic acid at the serum level in the elderly contributes to cell growth via mitochondrial dysfunction in colorectal cancer cell spheroids
title_short Methylmalonic acid at the serum level in the elderly contributes to cell growth via mitochondrial dysfunction in colorectal cancer cell spheroids
title_sort methylmalonic acid at the serum level in the elderly contributes to cell growth via mitochondrial dysfunction in colorectal cancer cell spheroids
topic Aging
Cancer
Glutamine
Mitochondria
Glycolytic system
Methylmalonic acid
url http://www.sciencedirect.com/science/article/pii/S2405580824002735
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AT chihomurakami methylmalonicacidattheserumlevelintheelderlycontributestocellgrowthviamitochondrialdysfunctionincolorectalcancercellspheroids
AT hideyayamamoto methylmalonicacidattheserumlevelintheelderlycontributestocellgrowthviamitochondrialdysfunctionincolorectalcancercellspheroids