Monthly Archives: June 2012

Distinct roles of different forms of vitamin E in DHA-induced apoptosis in triple-negative breast cancer cells

Ailian Xiong, Weiping Yu, Richa Tiwary, Bob G. Sanders and Kimberly Kline

Mol Nutr Food Res. 2012 Jun;56(6):923-34

Scope: Docosahexaenoic acid (DHA) has been shown to exhibit anticancer actions in vitro and in vivo in a variety of cancers. Here, we investigated the role for DHA in inducing apoptosis in triple-negative breast cancer (TNBC) and studied the mechanisms of action.

Methods and Results: DHA induces apoptosis as detected byAnnexinV-FITC/PI assay as well as induces cleavage of caspase-8 and -9, endoplasmic reticulum stress (ERS), and elevated levels of death receptor-5 (DR5) protein expression as detected by western blot assays. Chemical inhibitors of caspase-8 and -9 and small interfering RNAs (siRNAs) show DHA to induce ERS/CHOP/DR5-mediated caspase-8 and -9 dependent apoptosis. Furthermore, DHA induces elevated cellular levels of reactive oxygen species (ROS) and antioxidant; RRR-α-tocopherol (_T) blocked DHA-induced apoptotic events. In contrast to the antagonistic impact of   αT, gamma tocotrienol(γT3) was demonstrated to cooperate with DHA in inducing apoptotic events in TNBC cells.

Conclusion: Data, for the first time, demonstrate thatDHAinduces apoptosis in TNBC cells via activation of ERS/CHOP/DR5-mediated caspase-8 and -9 dependent pro-apoptotic events, and that different forms of vitamin E exhibit distinct effects on DHA-induced apoptosis; namely, inhibition by αT and enhancement by γT3.

Mechanism of radioprotection by δ-tocotrienol: Pharmacokinetics, pharmacodynamics and modulation of signalling pathways

Satyamitra M, Ney P, Graves J, Mullaney C, Srinivasan V.

Br J Radiol. 2012 Jun 6.

Objective: To investigate the correlation between in vivo δ-tocotrienol (DT3) pharmacokinetcs, pharmacodynamics and radiation protection, and to evaluate the effect of DT3 pre-treatment on radiation-induced alterations in apoptotic and autophagic pathways.Methods: We evaluated pharmacokinetics (plasma, 0.5 to 12 h) and pharmacodynamics (peripheral blood indices, day 3, 7, 10 and 14) after a single subcutaneous injection of 300 mg kg DT3 in unirradiated CD2F1 mice. Next, we monitored 30-day post-irradiation survival (9.25 Gy) and haematopoietic recovery of DT3-treated mice (7 Gy) exposed to cobalt-60 γ irradiation. The effects of DT3 on irradiated bone marrow apoptosis and autophagy were determined by analyses of key caspases (3, 7, 9 and 8), beclin-1 and LC3 conversion.Results: Plasma concentration of DT3 reached ∼195 µM (Cmax) 1 h after injection (Tmax), and DT3 was eliminated from plasma 12 h later. In unirradiated mice, DT3 significantly increased white blood cells (WBCs), neutrophils, lymphocytes (day 3 post-DT3 injection) and platelets (day 7) by 1.5-2-fold, over vehicle-treated control. DT3 pre-treatment improved 30-day survival to 100% (∼15% in control) and accelerated recovery of reticulocytes, platelets, WBCs, neutrophils, lymphocytes and monocytes in peripheral blood. DT3 reduced activation of caspase-8, caspases-3 and -7, inherent to apoptosis, while increasing autophagy-related beclin-1 expression in irradiated bone marrow.Conclusion: These data indicate that DT3 stimulates multilineage haematopoiesis, protects against radiation-induced apoptosis downstream of the mitochondria and stimulates cytoprotective autophagy. Apart from a potent antioxidant activity, DT3 may elicit survival advantage following irradiation by enhancing haematopoiesis and modulating signalling pathways.

Gamma Tocotrienol E Can Help Asthma

Byron J. Richards

Tocotrienols are a unique form of vitamin E that possess many biologically active properties that plain vitamin E does not.  Researchers have now shown that gamma tocotrienol can influence gene signals of immune cells in the lungs in a way that prevents key problems involved with the pathogenesis of asthma.

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