Apoptosis Induction via ATM Phosphorylation, Cell Cycle Arrest, and ER Stress by Goniothalamin and Chemodrugs Combined Effects on Breast Cancer-Derived MDA-MB-231 Cells

摘要: Goniothalamin (GTN), a styryl-lactone, exhibits inhibitory effects on many kinds of cancer cells in vitro. The objectives this study were to investigate the anticancer activities GTN and molecular signaling pathways associated with cell death human breast MDA-MB-231 line. inhibited growth cells. Apoptosis was confirmed by annexin V-FITC PI staining, apoptotic morphology observed microscopy. Reduction mitochondrial transmembrane potential enhanced caspases found GTN-treated significantly altered apoptosis-related protein expressions, including Noxa, PUMA, Bax, Bim, Bad, Bcl-2, Bcl-xL, DIABLO, which related gene expression levels. Mitochondrial calcium released cytosol ER stress proteins increased, correlated increases induced hydrogen peroxide superoxide anion radicals cycle arrest G2/M phase, phosphorylation ATM expression. Moreover, had synergistic when combined cyclophosphamide, 5-fluorouracil, paclitaxel, vinblastine, additive effect methotrexate through enzyme-acceleration. In conclusion, goniothalamin-induced apoptosis occurred via intrinsic extrinsic pathways, along stress. These provide new targeted drug strategies for advancements medicine.