title: Tocotrienol combination therapy results in synergistic anticancer response.
abstract: Vitamin E represents a family of compounds that is divided into two subgroups called tocopherols and tocotrienols, which act as important antioxidants that regulate peroxidation reactions and control free-radical production within the body. However, many of the biological effects of vitamin E are mediated independently of its antioxidant activity. Although tocopherols and tocotrienols have the same basic chemical structure characterized by a long phytyl chain attached to a chromane ring, only tocotrienols display potent anticancer activity, by modulating multiple intracellular signaling pathways associated with tumor cell proliferation and survival, and combination therapy with other chemotherapeutic agents result in a synergistic anticancer response. Combination therapy is most effective when tocotrienols are combined with agents that have complementary anticancer mechanisms of action. These findings strongly suggest that the synergistic antiproliferative and apoptotic effects demonstrated by combined low dose treatment of γ-tocotrienol with other chemotherapeutic agents may provide significant health benefits in the prevention and/or treatment of breast cancer in women, while at the same time avoiding tumor resistance and toxic side effects associated with high dose monotherapy.
authors.affiliation: College of Pharmacy, 700 University Avenue, University of Louisiana at Monroe, Monroe, LA 71209-0470, USA. sylvester@ulm.edu
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sylvester
authors.forename: Vikram B
authors.initials: VB
authors.lastname: Wali
authors.forename: Sunitha V
authors.initials: SV
authors.lastname: Bachawal
authors.forename: Amit B
authors.initials: AB
authors.lastname: Shirode
authors.forename: Nehad M
authors.initials: NM
authors.lastname: Ayoub
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Akl
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D004357:Drug Synergism; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D024508:Tocotrienols / Q000008:administration & dosage*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047428:Protein Kinase Inhibitors; D024508:Tocotrienols; D020794:Receptor Protein-Tyrosine Kinases