Garlic arrests MDA-MB-435 cancer cells in mitosis, phosphorylates the proapoptotic BH3-only protein BimEL 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 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.
Lund
T
T
Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo 0310, Norway. terjelu@radium.uio.no
Stokke
T
T
Olsen
Ø E
ØE
Fodstad
Ø
Ø
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005737:Garlic; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins; D008565:Membrane Proteins; D010936:Plant Extracts; D011518:Proto-Oncogene Proteins