Oxidative stress plays a pivotal role in the pathogenesis of several chronic diseases and antioxidants may represent potential tools for the prevention of these diseases. Here, we investigated the antioxidant efficiency of different tocotrienol isoforms (alpha-, delta-, gamma-tocotrienols), and that of FeAox-6, a novel synthetic compound which combines, by a stable covalent bond, the chroman head of vitamin E and a polyisoprenyl sequence of four conjugated double bonds into a single molecule. The antioxidant efficiency was evaluated as the ability of the compounds to inhibit lipid peroxidation, reactive oxygen species (ROS) production, heat shock protein (hsp) expression in rat liver microsomal membranes as well as in RAT-1 immortalized fibroblasts challenged with different free radical sources, including 2,2′-azobis(2-amidinopropane) (AAPH), tert-butyl hydroperoxide (tert-BOOH) and H2O2. Our results show that individual tocotrienols display different antioxidant potencies. Irrespective of the prooxidant used, the order of effectiveness was:delta-tocotrienol > gamma-tocotrienol = alpha-tocotrienol in both isolated membranes and intact cells. This is presumably due to the decreased methylation of delta-tocotrienol chromane ring, which allows the molecule to be more easily incorporated into cell membranes. Moreover, we found that FeAox-6 showed an antioxidant potency greater than that of delta-tocotrienol. Such an efficiency seems to depend on the concomitant presence of a chromane ring and a phytyl chain in the molecule, which because of four conjugated double bonds, may induce a greater mobility and a more uniform distribution within cell membrane. In view of these results, FeAox-6 represents a new potential preventive agent in chronic diseases in which oxidative stress plays a pathogenic role.
Monthly Archives: July 2006
Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptosis selectively in human prostate cancer cells
Srivastava JK, Gupta S.
Biochem Biophys Res Commun. 2006 Jul 28;346(2):447-53. Epub 2006 Jun 2.
One of the requisite of cancer chemopreventive agent is elimination of damaged or malignant cells through cell cycle inhibition or induction of apoptosis without affecting normal cells. In this study, employing normal human prostate epithelial cells (PrEC), virally transformed normal human prostate epithelial cells (PZ-HPV-7), and human prostate cancer cells (LNCaP, DU145, and PC-3), we evaluated the growth-inhibitory and apoptotic effects of tocotrienol-rich fraction (TRF) extracted from palm oil. TRF treatment to PrEC and PZ-HPV-7 resulted in almost identical growth-inhibitory responses of low magnitude. In sharp contrast, TRF treatment resulted in significant decreases in cell viability and colony formation in all three prostate cancer cell lines. The IC(50) values after 24h TRF treatment in LNCaP, PC-3, and DU145 cells were in the order 16.5, 17.5, and 22.0 microg/ml. TRF treatment resulted in significant apoptosis in all the cell lines as evident from (i) DNA fragmentation, (ii) fluorescence microscopy, and (iii) cell death detection ELISA, whereas the PrEC and PZ-HPV-7 cells did not undergo apoptosis, but showed modestly decreased cell viability only at a high dose of 80 microg/ml. In cell cycle analysis, TRF (10-40 microg/ml) resulted in a dose-dependent G0/G1 phase arrest and sub G1 accumulation in all three cancer cell lines but not in PZ-HPV-7 cells. These results suggest that the palm oil derivative TRF is capable of selectively inhibiting cellular proliferation and accelerating apoptotic events in prostate cancer cells. TRF offers significant promise as a chemopreventive and/or therapeutic agent against prostate cancer.
BACKGROUND: Vitamin E is a generic term used to describe the many derivatives of tocol and tocotrienol. It is the major lipid-soluble antioxidant in the skin and has been used as treatment for many skin conditions, including scarring. Studies have shown that vitamin E provides no benefit to the cosmetic outcome of scars.
METHODS:The authors constructed and distributed a questionnaire among staff and students at their institution. Their aim was to determine patterns of use and prescription of vitamin E among staff and students and to determine the understanding of the properties and biological functions of vitamin E.
RESULTS: Questionnaires were completed by 208 staff and students, including 110 nonconsultant hospital doctors (52.89 percent), 61 nurses (29.33 percent), and 27 medical students (12.98 percent). Nearly 68 percent thought that vitamin E could be of use in improving the cosmetic appearance of scars, while 25 percent actually recommended vitamin E to patients to improve the cosmetic outcome of scars. Just under 40 percent were aware of the biological function of vitamin E, while 16.35 percent thought vitamin E had absolutely no effect on scarring. Of respondents, 21.64 percent had used vitamin E for their own scars; 31.11 percent of these said it was suggested by a doctor, while 6.67 percent said a pharmacist suggested it.
CONCLUSIONS: Without scientific basis, health professionals continue to recommend vitamin E for use on scars. Such recommendations should not be made in the absence of evidence-based medicine.
The natural vitamin E tocotrienol (TCT) possesses biological properties not shared by tocopherols (TCP). Nanomolar alpha-TCT, not alpha-TCP, is potently neuroprotective (JBC 275:13049; 278:43508; Stroke 36:2258). The report that the affinity of TTP to bind (alpha-TCT is an order of magnitude lower than that for alpha-TCP questions the bioavailability of orally taken TCT to tissues. Oral supplementation of TCT for 3 years in nine generations of female and male rat was studied. Ten vital organs were examined. To gain insight into the turnover of alpha-TCT in tissues, a subset of supplemented rats was moved to vitamin E deficient diet for 7 weeks. Orally supplemented alpha-TCT was delivered to all vital organs including the brain and spinal cord in significant amounts. In organs such as the skin, adipose and gonads the maximum level of alpha-TCT achieved in response to supplementation was folds higher than baseline values of alpha-TCP in rats maintained on laboratory chow. Females had higher levels of alpha-TCT compared to matched tissues of corresponding males. To gain insight into how quickly alpha-TCT is metabolized in the tissues, washout of alpha-TCT from vital organs was examined. alpha-TCT accumulated in vital organs over more than 2 years was almost completely lost in less than 2 months when the supplementation was stopped. This is in sharp contrast with findings related to alpha-TCP retention. The ability of long-term oral supplementation to maintain and elevate alpha-TCT levels in vital organs together with the rapid elimination of the intact vitamin from all organs studied underscores the need for continuous oral supplementation of TCT.