title: Induction of DNA damage and caspase-independent programmed cell death by vitamin E.
abstract: Vitamin E comprises 8 functionally unique isoforms and may be a suitable candidate for the adjuvant treatment of prostate cancer. In this study, we examined the ability of 2 vitamin E isoforms [α-tocotrienol (γ-TT) and δ-tocotrienol (δ-TT)] and 4 synthetic derivatives [γ- and δ-tocotrienol succinate (γ-TS, δ-TS), α-tocopheryl polyethylene glycol succinate (TPGS), and α-tocopheryl polyethylene glycol ether (TPGS-e)] of vitamin E to induce cell death in AR- (DU145 and PC-3) and AR+ (LNCaP) prostate cancer cell lines. Our results show that δ-TT and TPGS-e are the most effective isoform and synthetic derivative, respectively, of all compounds examined. Overall, the results of our study suggest that isoforms and synthetic derivatives of vitamin E have the potency to trigger both caspase-dependent and -independent DNA damage and dominant caspase-independent programmed cell death. The capacity of vitamin E to trigger caspase-independent programmed cell death suggests that it may be useful in the chemotherapy of prostate cancer since it may prevent the tumor resistance commonly associated with the use of classical chemotherapeutic agents that trigger caspase-dependent programmed cell death.
authors.affiliation: Yasoo Health, Ltd., Nicosia, Cyprus. constantinou.co@unic.ac.cy
authors.forename: C
authors.initials: C
authors.lastname: Constantinou
authors.forename: C M
authors.initials: CM
authors.lastname: Neophytou
authors.forename: P
authors.initials: P
authors.lastname: Vraka
authors.forename: J A
authors.initials: JA
authors.lastname: Hyatt
authors.forename: K A
authors.initials: KA
authors.lastname: Papas
authors.forename: A I
authors.initials: AI
authors.lastname: Constantinou
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007536:Isomerism; D008297:Male; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D024508:Tocotrienols; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D024508:Tocotrienols; D014810:Vitamin E; C082097:tocotrienol, delta; D011092:Polyethylene Glycols; D005047:Etoposide; C082032:tocotrienol, alpha; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D020169:Caspases; C014225:tocophersolan