Department of Chemical Engineering & Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan, R.O.C.
Division of Urology, Department of Surgery, E-Da Cancer Hospital, Kaohsiung, Taiwan, R.O.C.
Anticancer Res. 2024 May;44(5):1963-1971. doi: 10.21873/anticanres.16999.
BACKGROUND/AIM: Cancer cachexia is a wasting syndrome that has a devastating impact on the prognosis of patients with cancer. It is well-documented that pro-inflammatory cytokines are involved in the progression of this disorder. Therefore, this study was conducted to investigate the protective effect of taurine, an essential nonprotein amino acid with great anti-inflammatory properties, in attenuating muscle atrophy induced by cancer.
Conditioned media (CM) derived from T24 human bladder carcinoma cells with or without 5 mM taurine were incubated with human skeletal muscle cells (HSkMCs) and their differentiation was examined. The intracellular reactive oxygen species (ROS), morphology, and the catabolic pathway were monitored.
T24-derived CM with high levels of TNF-α and IL-6 caused aberrant ROS accumulation and formation of atrophic myotubes by HSkMCs. In T24 cancer cells, taurine significantly inhibited the production of TNF-α and IL-6. In HSkMCs, taurine increased ROS clearance during differentiation and preserved the myotube differentiation ability impaired by the inflammatory tumor microenvironment. In addition, taurine ameliorated myotube atrophy by regulating the Akt/FoxO1/MuRF1 and MAFbx signaling pathways.
Taurine rescues cancer-induced atrophy in human skeletal muscle cells by ameliorating the inflammatory tumor microenvironment. Taurine supplementation may be a promising approach for intervening with the progression of cancer cachexia.
背景/目的:癌症恶病质是一种消耗综合征,对癌症患者的预后有毁灭性的影响。有大量文献记载促炎细胞因子参与了这种疾病的进展。因此,本研究旨在探讨牛磺酸(一种具有强大抗炎特性的必需非蛋白氨基酸)对减轻癌症引起的肌肉萎缩的保护作用。
用或不用 5mM 牛磺酸的 T24 人膀胱癌细胞的条件培养基(CM)孵育人骨骼肌细胞(HSkMCs),并检测其分化情况。监测细胞内活性氧(ROS)、形态和分解代谢途径。
T24 衍生的 CM 中 TNF-α 和 IL-6 水平较高,导致 HSkMCs 中异常的 ROS 积累和萎缩肌管形成。在 T24 癌细胞中,牛磺酸显著抑制 TNF-α 和 IL-6 的产生。在 HSkMCs 中,牛磺酸在分化过程中增加了 ROS 的清除,并保持了由炎症肿瘤微环境损害的肌管分化能力。此外,牛磺酸通过调节 Akt/FoxO1/MuRF1 和 MAFbx 信号通路改善肌管萎缩。
牛磺酸通过改善炎症肿瘤微环境来挽救人类骨骼肌细胞中的癌症诱导性萎缩。牛磺酸的补充可能是干预癌症恶病质进展的一种有前途的方法。