A novel quinazolinone derivative induces cytochrome c interdependent apoptosis and autophagy in human leukemia MOLT-4 cells

Publication date: Available online 12 August 2014 Source:Toxicology Reports Author(s): Suresh Kumar , Anup Singh Pathania , Santosh Kumar Guru , Nagaraju Mupparapu , Ajay Kumar , Fayaz Malik , Sandip B. Bharate , Naved Ahmed Qazi , Ram A. Vishwakarma , Shashi Bhushan Crosstalk between apoptosis and autophagy is budding as one of the novel strategies in the cancer therapeutics. The present study tinted towards the interdependence of autophagy and apoptosis induce by a novel quinazolinone derivative 2, 3-Dihydro-2-(quinoline-5-yl) quinazolin-4(1H)-one structure [DQQ] in human leukemia MOLT-4 cells. DQQ induces cytochrome c arbitrated apoptosis and autophagy in MOLT-4 cells. Apoptosis induces by DQQ was confirmed through a battery of assay e.g. cellular and nuclear microscopy, annexin-V assay, cell cycle analysis, loss of mitochondrial membrane potential and immune-expression of cytochrome c, caspases and PARP. Furthermore, acridine orange staining, LC3 immunofluorescence and western blotting of key autophagy proteins revealed the autophagic potential of DQQ. A universal caspase inhibitor, Z-VAD-FMK and cytochrome c silencing, strongly inhibited the DQQ induce autophagy and apoptosis. Beclin1 silencing through siRNA partially reversed the cell death, which was not as significant as by cytochrome c silencing. Although, it partially reversed the PARP cleavage induced by DQQ, indicating the role of autophagy in the regulation of apoptosis. The present study first time...
Source: Toxicology Reports - Category: Toxicology Source Type: research