Demethoxycurcumin mediated targeting of MnSOD leading to activation of apoptotic pathway and inhibition of Akt/NF-κB survival signalling in human glioma U87 MG cells.

摘要: Abstract Earlier, we reported that Demethoxycurcumin (DMC) suppressed the growth of human glioma U87 MG cells by downregulation Bcl-2 expression. In present work, investigated DMC induced reactive oxygen species (ROS) mediated anti-proliferative and apoptotic effects in cells. Exposure to growth-suppressive concentrations (0–50 μg/ml) resulted ROS generation concomitant increase apoptosis. The major oxidative was superoxide anion radical (O2− ). DMC-induced anti-proliferation Akt/NF-κB signalling inhibition apoptosis through caspase-8 9 activation. silico molecular docking analysis showed that, amino acid residues His30, Tyr34, Asn37, Ala63, Asn67, His74, Trp123, Asp159 active site mitochondrial SOD (MnSOD) interacted with DMC. Furthermore, complex MnSOD-DMC found be more stable as compared native MnSOD MD simulations. study, have demonstrated for first time using cell line (a) establishes π-π interactions Tyr 34 Trp 161 putative inhibit its activity, generating ) regulate survival proteins leading antiproliferative events (b) induces effect via pathway (c) contributes caspase-9 activation release cytochrome c. exploring death U 87 line, revealed a novel mechanism DMC-mediated accumulation anions trigger pathways induction