Induction of caspase-independent programmed cell death by vitamin E natural homologs and synthetic derivatives.
Current observations in the literature suggest that vitamin E may be a suitable candidate for cancer chemotherapy. To investigate this further, we examined the ability of the vitamin E natural homologs [alpha-, beta-, gamma-, delta-tocopherols (alpha-TOC, beta-TOC, gamma-TOC, delta-TOC) and alpha-, beta-, gamma-, delta-tocotrienols (alpha-TT, beta-TT, gamma-TT, delta-TT)] and their corresponding succinate synthetic derivatives [alpha-, beta-, gamma-, delta-tocopheryl succinates and alpha-, beta-, gamma-, delta-tocotrienyl succinates (alpha-TS, beta-TS, gamma-TS, delta-TS)] to induce cell death in AR- (DU145 and PC3) and AR+ (LNCaP) prostate cancer cell lines. The most effective of all the natural homologs of vitamin E was determined to be delta-TT, whereas delta-TS was the most potent of all the natural and synthetic compounds of vitamin E examined. Both gamma-TT and delta-TT induced caspase activity selectively in AR+ LNCaP cells, suggesting a possible role for AR for the activation of caspase-dependent programmed cell death (CD-PCD). More important, however, gamma-TT, delta-TT, gamma-TS, and delta-TS activated dominant caspase-independent programmed cell death (CI-PCD) in all prostate cancer cell lines examined. Thus, vitamin E homologs and synthetic derivatives may find applications in the treatment of prostate tumors that are resistant to caspase-activating therapeutic agents.
Constantinou
Constantina
C
Yasoo Health Ltd., Nicosia, Cyprus.
Hyatt
John Anthony
JA
Vraka
Panayiota S
PS
Papas
Andreas
A
Papas
Konstantinos A
KA
Neophytou
Constantinos
C
Hadjivassiliou
Vicky
V
Constantinou
Andreas I
AI
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D031212:Bixaceae / Q000737:chemistry; D002338:Carotenoids / Q000737:chemistry; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D020128:Inhibitory Concentration 50; D007536:Isomerism; D008297:Male; D000073878:Palm Oil; D010936:Plant Extracts / Q000737:chemistry; D010938:Plant Oils / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism; D013997:Time Factors; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology
C410798:AR protein, human; D000972:Antineoplastic Agents, Phytogenic; D061945:Caspase Inhibitors; D010936:Plant Extracts; D010938:Plant Oils; D011944:Receptors, Androgen; D014810:Vitamin E; C082097:tocotrienol, delta; D002338:Carotenoids; D000073878:Palm Oil; C054041:annatto; D020169:Caspases