Tanaka Arowu R, Murakami Chiho, Yamamoto Hideya
Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami Ward, Hiroshima City, Hiroshima, 731-0153, Japan.
Biochem Biophys Rep. 2025 Jan 9;41:101909. doi: 10.1016/j.bbrep.2024.101909. eCollection 2025 Mar.
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.
甲基丙二酸（MMA）是在丙酸盐和支链氨基酸代谢过程中产生的一种小分子。最近，有报道称MMA的血液浓度会随着年龄增长而升高，并促进肺癌转移。然而，关于其对肺癌以外其他癌症的影响却知之甚少。在本研究中，我们检测了MMA对结直肠癌细胞球体的影响。我们发现，MMA在老年人可呈现的生理浓度下促进了结直肠癌细胞球体的增殖，并诱导线粒体活性氧生成，进而影响细胞生长的促进作用。MMA处理还会诱导糖酵解系统的代谢转变。这些结果表明，MMA可能通过降低线粒体功能、诱导代谢转变来促进癌细胞增殖，并为衰老对癌症的影响提供了新的见解。
