Targeting apoptosis by 1,2-diazole through regulation of EGFR, Bcl-2 and CDK-2 mediated signaling pathway in human non-small cell lung carcinoma A549 cells
| Autor: | Perumal Elangovan, Venugopal Vinod Prabhu, Sivasithambaram Niranjali Devaraj, Kunnathur Murugesan Sakthivel |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell cycle checkpoint Lung Neoplasms Cell Survival Cell 03 medical and health sciences 0302 clinical medicine Cyclin-dependent kinase Carcinoma Non-Small-Cell Lung Genetics medicine Humans Epidermal growth factor receptor Lung cancer Cell Proliferation A549 cell biology Cell Cycle Cyclin-Dependent Kinase 2 Cancer General Medicine medicine.disease Antineoplastic Agents Phytogenic ErbB Receptors Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 A549 Cells 030220 oncology & carcinogenesis biology.protein Cancer research Pyrazoles Signal transduction Signal Transduction |
| Zdroj: | Gene. 679 |
| ISSN: | 1879-0038 |
| Popis: | Lung cancer is the leading cause of cancer deaths worldwide and non-small cell lung carcinoma (NSCLC), a heterogeneous class of tumors, represents approximately 85% of all new lung cancer diagnosis. Conventional treatment options have limited efficacy because most cases are in the advanced stage at the time of diagnosis. The present study evaluates the anti-cancer activity of 1,2-diazole (pyrazole), a natural compound from mangrove plant Rhizophora apiculata (R.apiculata) on A549 lung carcinoma cells. In the present study the anti-cancer mechanism of pyrazole, was examined by the expression level of proteins Epidermal growth factor receptor (EGFR), Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2) and Cyclin-dependent kinase-2 (CDK-2) which are commonly associated with the cell signaling pathways that control cell survival and apoptosis, that could facilitate to develop a novel target and effective treatment approach for patients with NSCLC. Pyrazole significantly induced cell cycle arrest and initiated apoptosis through inhibition of downstream components of EGFR tyrosine kinase pathway. Pyrazole disrupts the mitochondrial membrane potential and modulated the protein levels of Bax and Bcl-2 which could probably lead to caspase-3 activation. Furthermore, Pyrazole suppresses the expression of CDK-2 resulting in cell cycle arrest at G1 phase and in the G1-S phase transition. Taken together, the current study provides new insight in to the precise molecular mechanisms responsible for the anti-cancer activity of pyrazole in NSCLC, A549 cells. The study opens an avenue for development of a natural compound as a potential therapeutic agent which could target cell signaling pathways to combat human NSCLC. |
| Databáze: | OpenAIRE |
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