A novel quinazolinone derivative induces cytochrome c interdependent apoptosis and autophagy in human leukemia MOLT-4 cells
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2014-01-01
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| Series: | Toxicology Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214750014000663 |
| _version_ | 1811231807585124352 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Suresh Kumar |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T10:52:16Z |
| format | Article |
| id | doaj.art-a8c0d634550a4cc49254ffe08ab72d29 |
| institution | Directory Open Access Journal |
| issn | 2214-7500 |
| language | English |
| last_indexed | 2024-04-12T10:52:16Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj.art-a8c0d634550a4cc49254ffe08ab72d292022-12-22T03:36:12ZengElsevierToxicology Reports2214-75002014-01-011C1013102510.1016/j.toxrep.2014.07.018A novel quinazolinone derivative induces cytochrome c interdependent apoptosis and autophagy in human leukemia MOLT-4 cellsSuresh Kumar0Santosh Kumar Guru1Anup Singh Pathania2Nagaraju Mupparapu3Ajay Kumar4Fayaz Malik5Sandip B. Bharate6Qazi Naveed Ahmed7Ram A. Vishwakarma8Shashi Bhushan9Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, IndiaAcademy of Scientific and Innovative Research (AcSIR), New Delhi 110001, IndiaAcademy of Scientific and Innovative Research (AcSIR), New Delhi 110001, IndiaAcademy of Scientific and Innovative Research (AcSIR), New Delhi 110001, IndiaCancer Pharmacology Division, Indian Institute of Integrative Medicine, CSIR, Jammu 180001, IndiaAcademy of Scientific and Innovative Research (AcSIR), New Delhi 110001, IndiaAcademy of Scientific and Innovative Research (AcSIR), New Delhi 110001, IndiaAcademy of Scientific and Innovative Research (AcSIR), New Delhi 110001, IndiaAcademy of Scientific and Innovative Research (AcSIR), New Delhi 110001, IndiaAcademy of Scientific and Innovative Research (AcSIR), New Delhi 110001, IndiaCrosstalk 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.http://www.sciencedirect.com/science/article/pii/S22147500140006632,3-Dihydro-2-(quinoline-5-yl) quinazolin-4(1H)-one structure [DQQ]AutophagyApoptosisCytochrome cCaspase |
| spellingShingle | 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 A novel quinazolinone derivative induces cytochrome c interdependent apoptosis and autophagy in human leukemia MOLT-4 cells Toxicology Reports 2,3-Dihydro-2-(quinoline-5-yl) quinazolin-4(1H)-one structure [DQQ] Autophagy Apoptosis Cytochrome c Caspase |
| title | A novel quinazolinone derivative induces cytochrome c interdependent apoptosis and autophagy in human leukemia MOLT-4 cells |
| title_full | A novel quinazolinone derivative induces cytochrome c interdependent apoptosis and autophagy in human leukemia MOLT-4 cells |
| title_fullStr | A novel quinazolinone derivative induces cytochrome c interdependent apoptosis and autophagy in human leukemia MOLT-4 cells |
| title_full_unstemmed | A novel quinazolinone derivative induces cytochrome c interdependent apoptosis and autophagy in human leukemia MOLT-4 cells |
| title_short | A novel quinazolinone derivative induces cytochrome c interdependent apoptosis and autophagy in human leukemia MOLT-4 cells |
| title_sort | novel quinazolinone derivative induces cytochrome c interdependent apoptosis and autophagy in human leukemia molt 4 cells |
| topic | 2,3-Dihydro-2-(quinoline-5-yl) quinazolin-4(1H)-one structure [DQQ] Autophagy Apoptosis Cytochrome c Caspase |
| url | http://www.sciencedirect.com/science/article/pii/S2214750014000663 |
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