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Cancer Lett ; 339(1): 116-27, 2013 Oct 01.
Article in English | MEDLINE | ID: mdl-23879968

ABSTRACT

The present study is the first to demonstrate the synergetic effect of statins (atorvastatin and simvastatin) and gamma-tocotrienol (γ-T3) on human malignant mesothelioma (MM). Statin + γ-T3 combinations induced greater cell growth inhibition more than each single treatment via inhibition of mevalonate pathway, a well-known target of both γ-T3 and statins. γ-T3 was necessary for endoplasmic reticulum stress markers CHOP and GRP78, whereas an intrinsic apoptotic marker, caspase 3 activation was induced only in the presence of statins. Overall, the combination of γ-T3 and statins could be useful for MM therapy and functions in a complementary style.


Subject(s)
Chromans/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Mesothelioma/metabolism , Vitamin E/analogs & derivatives , Apoptosis/drug effects , Atorvastatin , Caspase 3/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Chromans/administration & dosage , Chromans/toxicity , Drug Synergism , Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress/drug effects , Enzyme Activation/drug effects , Heptanoic Acids , Humans , Hydroxymethylglutaryl CoA Reductases/genetics , Hydroxymethylglutaryl CoA Reductases/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/toxicity , Mesothelioma/genetics , Metabolic Networks and Pathways/drug effects , Mevalonic Acid/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Pyrroles , Simvastatin , Vitamin E/administration & dosage , Vitamin E/pharmacology , Vitamin E/toxicity
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