Reference - Detail
| RRC ID | 42323 |
|---|---|
| Author | Roy MK, Thalang VN, Trakoontivakorn G, Nakahara K. |
| Title | Mahanine, a carbazole alkaloid from Micromelum minutum, inhibits cell growth and induces apoptosis in U937 cells through a mitochondrial dependent pathway. |
| Journal | Br J Pharmacol |
| Abstract |
1 Mahanine, a naturally occurring carbazole alkaloid in some Asian vegetables, has been shown to exhibit antimutagenicity, antimicrobial activity, cytotoxicity, and other biological properties. 2 In the present study, we investigated the effect of mahanine on the activation of the apoptotic pathway in human leukemia U937 cells. Various end points were used to screen for apoptosis: Morphological changes in cells, the relative numbers of viable and apoptotic cells; translocation of membrane bound phosphatidylserine and DNA analysis. 3 We found that mahanine-induced apoptosis in U937 cells involved activation of caspases, including caspase-3, release of cytochrome c into cytosol, loss of mitochondrial membrane permeability, and decreased levels of cellular ATP. 4 Pretreatment of cells with cyclosporine A, prior to/concomitant with exposure to mahanine, effectively prevented the deleterious effects of the alkaloid on cellular integrity and viability. 5 As mitochondrial permeability is known to be important in the regulation of cytochrome c release, our observations indicate that mitochondria are the principal target of mahanine. More specifically, we propose that mahanine causes the mitochondrial membranes to lose their permeability, resulting in caspase-3 activation and apoptosis. |
| Volume | 145(2) |
| Pages | 145-55 |
| Published | 2005-5-1 |
| DOI | 10.1038/sj.bjp.0706137 |
| PII | 0706137 |
| PMID | 15753952 |
| PMC | PMC1576126 |
| MeSH | Alkaloids / pharmacology* Antineoplastic Agents, Phytogenic / pharmacology* Apoptosis* Carbazoles / pharmacology* Caspase 3 Caspases / metabolism Cell Proliferation / drug effects Cell Survival / drug effects Cyclosporine / pharmacology Cytochromes c / metabolism DNA Fragmentation Enzyme Activation Humans Immunosuppressive Agents / pharmacology Ion Channels / metabolism Mitochondria / drug effects* Mitochondria / physiology Mitochondrial Membrane Transport Proteins Mitochondrial Permeability Transition Pore Nucleosomes / drug effects Nucleosomes / genetics Protein Transport Rutaceae* U937 Cells |
| IF | 7.73 |
| Times Cited | 46 |
| WOS Category | PHARMACOLOGY & PHARMACY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | U-937 DE-4(RCB0435) |