Taurine Protects Irinotecan-induced Muscle Dysfunction by Modulating Oxidative Stress and Endoplasmic Reticulum Stress in Human Skeletal Muscle Cells.

Abstract

Irinotecan is a key component of standard first-line treatment for metastatic colorectal cancer. However, irinotecan-induced muscle dysfunction is a contributing factor to cancer cachexia. Here, we present the protective effect of taurine, a conditionally essential amino acid with great antioxidant properties, in attenuating muscle dysfunction induced by irinotecan. Irinotecan (20 μg/ml) was added to human skeletal muscle cells (HSkMCs) with or without pre-treatment of taurine (5 mM). The effects of taurine and irinotecan on the viability, cytotoxicity, and differentiation ability of HSkMC myoblasts were examined. The intracellular reactive oxygen species (ROS) and endoplasmic reticulum stress (ERS) were also monitored. Irinotecan caused cytotoxicity of HSkMCs, while taurine pretreatment increased cell viability and inhibited adenylate kinase release significantly in both myoblasts and myotubes. During differentiation, taurine increased ROS clearance and preserved the myotube differentiation ability impaired by irinotecan. Irinotecan exposure resulted in the up-regulation of CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78). Taurine pretreatment could combat such irinotecan-induced ERS. The current in vitro study provides molecular evidence that taurine plays a beneficial role in protecting against irinotecan-induced muscle dysfunction by modulating oxidative stress and endoplasmic reticulum stress.