| 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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2014 |
| Předmět: |
|
| Zdroj: |
Toxicology Reports, Vol 1, Iss C, Pp 1013-1025 (2014) |
| Druh dokumentu: |
article |
| ISSN: |
2214-7500 |
| DOI: |
10.1016/j.toxrep.2014.07.018 |
| Popis: |
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: |
Directory of Open Access Journals |
| Externí odkaz: |
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