title: Sesamin synergistically potentiates the anticancer effects of γ-tocotrienol in mammary cancer cell lines.
abstract: γ-Tocotrienol and sesamin are phytochemicals that display potent anticancer activity. Since sesamin inhibits the metabolic degradation of tocotrienols, studies were conducted to determine if combined treatment with sesamin potentiates the antiproliferative effects of γ-tocotrienol on neoplastic mouse (+SA) and human (MCF-7 and MDA-MB-231) mammary cancer cells. Results showed that treatment with γ-tocotrienol or sesamin alone induced a significant dose-responsive growth inhibition, whereas combination treatment with these agents synergistically inhibited the growth of +SA, MCF-7 and MDA-MB-231 mammary cancer cells, while similar treatment doses were found to have little or no effect on normal (mouse CL-S1 and human MCF-10A) mammary epithelial cell growth or viability. However, sesamin synergistic enhancement of γ-tocotrienol-induced anticancer effects was not found to be mediated from a reduction in γ-tocotrienol metabolism. Rather, combined treatment with subeffective doses of γ-tocotrienol and sesamin was found to induce G1 cell cycle arrest, and a corresponding decrease in cyclin D1, CDK2, CDK4, CDK6, phospho-Rb, and E2F1 levels, and increase in p27 and p16 levels. Additional studies showed that the antiproliferative effect of combination treatment did not initiate apoptosis or result in a decrease in mammary cancer cell viability. Taken together, these findings indicate that the synergistic antiproliferative action of combined γ-tocotrienol and sesamin treatment in mouse and human mammary cancer cells is cytostatic, not cytotoxic, and results from G1 cell cycle arrest.
authors.affiliation: College of Pharmacy, University of Louisiana at Monroe, 700 University Ave, Monroe, LA 71291, USA.
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Akl
authors.forename: Nehad M
authors.initials: NM
authors.lastname: Ayoub
authors.forename: Bilal S
authors.initials: BS
authors.lastname: Abuasal
authors.forename: Amal
authors.initials: A
authors.lastname: Kaddoumi
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sylvester
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002839:Chromans / Q000008:administration & dosage / Q000494:pharmacology*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004149:Dioxoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002839:Chromans; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D004149:Dioxoles; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D017705:Lignans; D016160:Retinoblastoma Protein; D014810:Vitamin E; C013649:plastochromanol 8; C054125:sesamin