A novel quinazolinone derivative induces cytochrome
| Autor: | Suresh, Kumar, Santosh Kumar, Guru, Anup Singh, Pathania, Nagaraju, Mupparapu, Ajay, Kumar, Fayaz, Malik, Sandip B, Bharate, Qazi, Naveed Ahmed, Ram A, Vishwakarma, Shashi, Bhushan |
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| Rok vydání: | 2014 |
| Předmět: |
AO
acridine orange MMP mitochondrial membrane potential ZVAD(zVAD fmk) benzyloxycarbonyl-Val-Ala-Asp fluoro-methyl-ketone ATG autophagy related gene Cytochrome c Apoptosis MTT 3-(4 5-Dimethylthiazole-2-yl)-2 5-diphenyltetrazolium bromide Caspase Article PARP-1 poly(ADP-ribose) polymerase-1 PI propidium iodide 2 3-Dihydro-2-(quinoline-5-yl) quinazolin-4(1H)-one structure [DQQ] Rh-123 rhodamine-123 Autophagy LC3 microtubule-associated protein light chain 3 ComputingMethodologies_COMPUTERGRAPHICS |
| Zdroj: | Toxicology Reports |
| ISSN: | 2214-7500 |
| Popis: | Graphical abstract Crosstalk between apoptosis and autophagy is budding as one of the novel strategies in the cancer therapeutics. The present study tinted toward 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 portrays the negative feedback potential of cytochrome c regulated autophagy and the importance of quinazolinone derivative in discovery of novel anticancer therapeutics. |
| Databáze: | OpenAIRE |
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