Garlic arrests MDA-MB-435 cancer cells in mitosis, phosphorylates the proapoptotic BH3-only protein BimEL and induces apoptosis
| Autor: | T Lund, Øystein Fodstad, Trond Stokke, Ø E Olsen |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Programmed cell death Mitochondrion Biology Microtubules garlic Cell Line Tumor Proto-Oncogene Proteins Humans Phosphorylation Kinase activity Molecular Diagnostics Mitosis mitosis Bcl-2-Like Protein 11 Plant Extracts Kinase BimEL apoptosis Membrane Proteins food and beverages Cell biology Oncology Apoptosis Cancer cell Apoptosis Regulatory Proteins Carrier Proteins BH3 Interacting Domain Death Agonist Protein |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Components of garlic (Allium sativum) can cause disruption of microtubules, cell cycle arrest, and apoptosis in cancer cells. We show here that a water-soluble extract of garlic arrested MDA-MB-435 cancer cells in mitosis and caused apoptosis. The proapoptotic BH3-only, bcl-2 family protein BimEL, which in healthy cells can be tightly sequestered to the microtubule-associated dynein motor complex, was modified after garlic treatment. The main effect of garlic on BimEL was a considerable increase in a phosphorylated form of the protein. This phosphorylation(s), probably partly dependent on c-jun N-terminal kinase activity, promoted mitochondrial localisation of BimEL. Furthermore, inhibition of extracellular signal-regulated kinases 1/2 increased the amount of another form of BimEL present in the mitochondrial cellular fraction. Treatment of cells with the garlic compound diallyl disulphide had similar effects on BimEL. The results indicate that the apoptotic effect of garlic and a combination of garlic and the inhibitor of extracellular signal-regulated kinases 1/2 in MDA-MB-435 cells partly is due to modifications that are necessary for translocation of the proapoptotic protein BimEL to mitochondria where it executes its proapoptotic function. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|