Decursin enhances TRAIL-induced apoptosis through oxidative stress mediated- endoplasmic reticulum stress signalling in non-small cell lung cancers.

摘要: BACKGROUND AND PURPOSE The TNF-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent due to its remarkable ability selectively kill tumour cells. However, because most tumours exhibit resistance TRAIL-induced apoptosis, the development of combination therapies overcome TRAIL required for effective cancer therapy. EXPERIMENTAL APPROACH Cell viability and possible synergy between plant pyranocoumarin decursin was measured by MTT assay calcusyn software. Reactive oxygen species (ROS) apoptosis were using dichlorodihydrofluorescein annexin/propidium iodide in cell flow cytometry. Changes protein levels assessed with Western blotting. KEY RESULTS Combining markedly decreased increased TRAIL-resistant non-small-cell lung (NSCLC) lines. Decursin induced expression death receptor 5 (DR5). Inhibition DR5 attenuated apoptotic + treated NSCLC Interestingly, induction CCAAT/enhancer-binding homologues mediated through selective pancreatic endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) branch stress response pathway. Furthermore, enhancement PERK/ATF4 signalling ROS generation lines, but not normal human also down-regulated survivin Bcl-xL CONCLUSIONS IMPLICATIONS activated axis pathway, leading enhanced sensitivity partly via up-regulation DR5.