Apoptosis of non-small-cell lung cancer cell lines after paclitaxel treatment involves the BH3-only proapoptotic protein Bim
| Autor: | Hong-Ming Hu, Tarsem Moudgil, H J Ross, R Li |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
G2 Phase
Male Lung Neoplasms Paclitaxel Antineoplastic Agents Apoptosis Mitochondrion Microtubules Enzyme activator chemistry.chemical_compound Microtubule Carcinoma Non-Small-Cell Lung Cell Line Tumor Proto-Oncogene Proteins medicine Humans RNA Small Interfering Lung cancer neoplasms Molecular Biology Bcl-2-Like Protein 11 Chemistry Membrane Proteins Cell Biology medicine.disease Caspase Inhibitors Cell biology Mitochondria Enzyme Activation Proto-Oncogene Proteins c-bcl-2 Cell culture Caspases Female biological phenomena cell phenomena and immunity Signal transduction Tumor Suppressor Protein p53 Apoptosis Regulatory Proteins Carrier Proteins Cell Division Signal Transduction |
| Zdroj: | Cell death and differentiation. 12(3) |
| ISSN: | 1350-9047 |
| Popis: | A significant variation in susceptibility to paclitaxel-mediated killing was observed among a panel of short-term cultured non-small-cell lung cancer (NSCLC) cell lines. Susceptibility to killing by paclitaxel correlated with expression of the BH3-only protein, Bim, but not with other members of Bcl-2 family. NSCLC cell lines with the highest level of Bim expression are most susceptible to apoptosis induction after paclitaxel treatment. Forced expression of Bim increased paclitaxel-mediated killing of cells expressing an undetectable level of Bim. Conversely, knock down of Bim, but not Bcl-2 expression, decreased the susceptibility of tumor cells to paclitaxel-mediated killing. Similar observations were made using a panel of breast and prostate cancer cell lines. Paclitaxel impairs microtubule function, causes G2/M cell cycle blockade, mitochondria damage, and p53-independent apoptosis. These results established Bim as a critical molecular link between the microtubule poison, paclitaxel, and apoptosis. |
| Databáze: | OpenAIRE |
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