title: Gamma-tocopherol enhances apoptotic effects of lovastatin in human colorectal carcinoma cell line (HT29).
abstract: Recently, we found that lovastatin, a HMG-CoA reductase inhibitor, and gamma-tocopherol, one of the significant types of vitamin E in diet, additively induced apoptosis in a colorectal carcinoma cell line. In this study we mechanistically monitored the loss of mitochondrial membrane potential, amount of cytosolic cytochrome c and caspase 3 activity after treatment by lovastatin and gamma-tocopherol. HT29 cells were treated with different doses of lovastatin and gamma-tocopherol for 48 and 72 h. Lovastatin and gamma-tocopherol in combination induced the release of cytochrome c, caspase 3 activation, and loss of mitochondrial membrane potential more significantly compared to their controls. Our data showed that lovastatin plus gamma tocopherol potently induced mitochondrial membrane potential collapse, cytochrome c release along with caspase 3 activation that reveals the importance of targeting programmed cell death signaling at different points of its signaling pathway for cancer therapy.
authors.affiliation: a Department of Pharmacology and Toxicology, School of Pharmacy, Jundishapur University of Medical Sciences, Ahvaz, Iran and Cellular and Molecular Research Center, Jundishapur University of Medical Sciences , Ahvaz , Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Rezaei
authors.forename: Leila
authors.initials: L
authors.lastname: Zeidooni
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Hashemitabar
authors.forename: Sareh
authors.initials: S
authors.lastname: Razzazzadeh
authors.forename: Masoud
authors.initials: M
authors.lastname: Mahdavinia
authors.forename: Kosar
authors.initials: K
authors.lastname: Ghasemi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000473:pathology*; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology*; D015398:Signal Transduction; D024504:gamma-Tocopherol / Q000494:pharmacology*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D024504:gamma-Tocopherol; D045304:Cytochromes c; D008148:Lovastatin; C505407:CASP3 protein, human; D053148:Caspase 3