Phenethyl Isothiocyanate Suppresses Stemness in the Chemo- And Radio-Resistant Triple-Negative Breast Cancer Cell Line MDA-MB-231/IR Via Downregulation of Metadherin

摘要: Resistance to chemotherapy and radiation therapy is considered a major therapeutic barrier in breast cancer. Cancer stem cells (CSCs) play prominent role chemo radiotherapy resistance. The established radio-resistant triple-negative cancer (TNBC) cell line MDA-MB-231/IR displays greater CSC characteristics than the parental MDA-MB-231 cells. Escalating evidence demonstrates that metadherin (MTDH) associated with number of signaling pathways as well resistance, making it an attractive target. Kaplan-Meier plot analysis revealed correlation between higher levels MTDH shorter lifetimes TNBC patients. Moreover, there was positive CD44 expression Genome Atlas database. We demonstrate plays pivotal regulation stemness Knockdown resulted reduction population, aldehyde dehydrogenase activity, markers, including β-catenin, CD44+, Slug. In addition, knockdown increased reactive oxygen species (ROS) found phenethyl isothiocyanate (PEITC), well-known pro-oxidant phytochemical, suppressed through ROS modulation via downregulation MTDH. Co-treatment PEITC N-Acetylcysteine (a scavenger) caused alterations induced death markers. regulated at post-transcriptional level, which confirmed using cycloheximide, protein synthesis inhibitor.