Aranorosin and a novel derivative inhibit the anti-apoptotic functions regulated by Bcl-2
| Autor: | Mitsunobu Hara, Takayuki Nakashima, Yutaka Kanda, Rieko Tanaka, Yoshinori Yamashita |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Cell
Biophysics Apoptosis Mitochondrion Biochemistry medicine Humans Spiro Compounds fas Receptor Cycloheximide Furans Molecular Biology Caspase Cell Nucleus Membrane potential biology Cell Biology Cell biology medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 Cell culture biology.protein Antibody Function (biology) HeLa Cells |
| Zdroj: | Biochemical and Biophysical Research Communications. 377:1085-1090 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2008.10.112 |
| Popis: | Bcl-2 is an intracellular membrane protein that prevents cells from undergoing apoptosis in response to various cell-death signals. It negatively regulates mitochondrial outer membrane permeabilization, which is responsible for the release of apoptogenic factors and the subsequent activation of caspases. A microbial metabolite, aranorosin, was identified as an inhibitor of the anti-apoptotic function of Bcl-2. Based on its structure, a more potent derivative, K050, was synthesized. Apoptosis could be induced in a cell line that overexpressed Bcl-2 when cells were treated with an anti-Fas antibody in addition to K050, at sub-micromolar concentrations. Furthermore, K050 inhibited anti-apoptotic functions regulated by Bcl-2, resulting in a Fas-triggered mitochondrial transmembrane potential loss, the activation of caspase-9, and a morphological change to apoptosis. Inhibition of cell-based function of Bcl-2 and its anti-apoptotic effects could serve as useful pharmacological effects. Thus, a novel aranorosin derivative, K050, could be a potent therapeutic agent against Bcl-2-overexpressing human malignancies. |
| Databáze: | OpenAIRE |
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