title: Synergistic effect of combined treatment with gamma-tocotrienol and statin on human malignant mesothelioma cells.
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.
authors.affiliation: Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8675, Japan.
authors.forename: Guligena
authors.initials: G
authors.lastname: Tuerdi
authors.forename: Saki
authors.initials: S
authors.lastname: Ichinomiya
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sato
authors.forename: Sana
authors.initials: S
authors.lastname: Siddig
authors.forename: Eriko
authors.initials: E
authors.lastname: Suwa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Iwata
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yano
authors.forename: Koichi
authors.initials: K
authors.lastname: Ueno
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004357:Drug Synergism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006538:Heptanoic Acids; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008798:Mevalonic Acid / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011758:Pyrroles; D019821:Simvastatin; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D002839:Chromans; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011758:Pyrroles; D014810:Vitamin E; C013649:plastochromanol 8; D000069059:Atorvastatin; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D053148:Caspase 3; D008798:Mevalonic Acid
keywords: Apoptosis; Gamma tocotrienol; Mesothelioma; Mevalonate pathway; Statin