Garlic arrests MDA-MB-435 cancer cells in mitosis, phosphorylates the proapoptotic BH3-only protein Bim(EL) and induces apoptosis

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 Bim(EL), 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 Bim(EL) 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 Bim(EL). Furthermore, inhibition of extracellular signal-regulated kinases 1/2 increased the amount of another form of Bim(EL) present in the mitochondrial cellular fraction. Treatment of cells with the garlic compound diallyl disulphide had similar effects on Bim(EL). 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 Bim(EL) to mitochondria where it executes its proapoptotic function.