Marine steroid derived from Acropora formosa enhances mitochondrial-mediated apoptosis in non-small cell lung cancer cells
| Autor: | Ravikumar Vilwanathan, Revathidevi Sundaramoorthy, Rajaram Rajendran, Varunkumar Krishnamoorthy, Ramalingam Vaikundamoorthy |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Programmed cell death Lung Neoplasms Cell cycle checkpoint DNA repair Antineoplastic Agents Apoptosis Biology 03 medical and health sciences 0302 clinical medicine Carcinoma Non-Small-Cell Lung Animals Humans Inner mitochondrial membrane Cholestenones A549 cell Tumor Necrosis Factor-alpha Gene Expression Profiling Interleukin-8 Intrinsic apoptosis NF-kappa B Cell Cycle Checkpoints General Medicine Anthozoa Mitochondria Neoplasm Proteins Cell biology 030104 developmental biology A549 Cells Cell culture 030220 oncology & carcinogenesis Immunology Tumor Suppressor Protein p53 Apoptosis Regulatory Proteins Reactive Oxygen Species |
| Zdroj: | Tumor Biology. 37:10517-10531 |
| ISSN: | 1423-0380 1010-4283 |
| DOI: | 10.1007/s13277-016-4947-8 |
| Popis: | p53 pathway has been revealed to mediate cellular stress responses and trigger DNA repair, cell cycle arrest, senescence, and apoptosis. We isolated 2-ethoxycarbonyl-2-β-hydroxy-A-nor-cholest-5-ene-4one (ECHC) from butanol extracts of scleractinian coral Acropora formosa and reported its potential antioxidant and antimicrobial activity as well as less toxicity against zebrafish Danio rerio. In the present study, we intend to explore p53-mediated apoptosis pathway enhanced by ECHC in A549 human non-small cell lung cancer cell lines. This report shows that ECHC increases ROS generation and sensitizes mitochondrial membrane that leads to the release of cytochrome C (Cyto C) into cytosol. Further, ECHC decreases the expression of antiapoptotic genes such as TNF-α, IL-8, Bcl2, MMP2, and MMP9 which are actively involved in cancer cell proliferation, invasion, and metastasis etc. It also increases the expression of apoptotic genes Cyto C, Bax, and p21, which are responsible for cell cycle arrest and cell death. The tumor suppressor p53 was also observed to be upregulated during ECHC treatment in untransformed cells and was more likely to result in cell cycle arrest, senescence, and apoptosis. Finally, ECHC also down regulates the expression of caspase-9 and caspase-3 which are the death stage of intrinsic apoptosis. Our findings suggested that ECHC enhances ROS generation and mitochondrial sensitization determines the threshold for irreversible p53-mediated intrinsic apoptosis pathway. |
| Databáze: | OpenAIRE |
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