Combination Effect of δ-Tocotrienol and γ-Tocopherol on Prostate Cancer Cell Growth.

Tocotrienols (T3s) and tocopherols (Tocs) are both members of the vitamin E family. It is known that δ-tocotrienol (δ-T3) has displayed the most potent anti-cancer activity amongst the tocotrienols. On the other hand, γ-tocopherol (γ-Toc) is reported to have a protective effect against prostate cancer. Therefore, we investigated whether the combination of γ-Toc and δ-T3 could strengthen the inhibitory effect of δ-T3 on prostate cancer cell growth. In this study the effect of combined δ-T3 (annatto T3 oil) and γ-Toc (Tmix, γ-Toc-rich oil) therapy was assessed against human androgen-dependent prostate cancer cells (LNCaP). We found that combined treatment of δ-T3 (10 μM) and γ-Toc (5 μM) resulted in reinforced anti-prostate cancer activity. Specifically, cell cycle phase distribution analysis revealed that in addition to G1 arrest caused by the treatment with δ-T3, the combination of δ-T3 with γ-Toc induced G2/M arrest. Enhanced induction of apoptosis by the combined treatment was also observed. These findings indicate that combination of δ-T3 and γ-Toc significantly inhibits prostate cancer cell growth due to the simultaneous cell cycle arrest in the G1 phase and G2/M phase.

[1]  P. Sylvester,et al.  Antiproliferative effects of γ-tocotrienol are associated with lipid raft disruption in HER2-positive human breast cancer cells. , 2016, The Journal of nutritional biochemistry.

[2]  T. Yang,et al.  Insights into Chemoresistance of Prostate Cancer , 2015, International journal of biological sciences.

[3]  Hiroshi Nishimoto,et al.  An updated report on the trends in cancer incidence and mortality in Japan, 1958-2013. , 2015, Japanese journal of clinical oncology.

[4]  C. Mathers,et al.  Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 , 2015, International journal of cancer.

[5]  F. Mollinedo,et al.  Lipid rafts as major platforms for signaling regulation in cancer. , 2015, Advances in biological regulation.

[6]  T. Yano,et al.  Annatto Tocotrienol Induces a Cytotoxic Effect on Human Prostate Cancer PC3 Cells via the Simultaneous Inhibition of Src and Stat3. , 2015, Journal of nutritional science and vitaminology.

[7]  H. Ahsan,et al.  Pharmacological potential of tocotrienols: a review , 2014, Nutrition & Metabolism.

[8]  Shiyong Wu,et al.  Lipid raft: A floating island of death or survival. , 2012, Toxicology and applied pharmacology.

[9]  R. DiPaola,et al.  Inhibitory Effect of a γ-Tocopherol-Rich Mixture of Tocopherols on the Formation and Growth of LNCaP Prostate Tumors in Immunodeficient Mice , 2011, Cancers.

[10]  B. Aggarwal,et al.  Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases. , 2010, Biochemical pharmacology.

[11]  K. Nakagawa,et al.  alpha-Tocopherol attenuates the cytotoxic effect of delta-tocotrienol in human colorectal adenocarcinoma cells. , 2010, Biochemical and biophysical research communications.

[12]  Y. Yap,et al.  In vivo Evidence of γ-Tocotrienol as a Chemosensitizer in the Treatment of Hormone-Refractory Prostate Cancer , 2010, Pharmacology.

[13]  A. Constantinou,et al.  Induction of Caspase-Independent Programmed Cell Death by Vitamin E Natural Homologs and Synthetic Derivatives , 2009, Nutrition and cancer.

[14]  R. Newman,et al.  Gamma Tocopherol Upregulates the Expression of 15-S-HETE and Induces Growth Arrest Through a PPAR Gamma-Dependent Mechanism in PC-3 Human Prostate Cancer Cells , 2009, Nutrition and cancer.

[15]  K. Nakagawa,et al.  delta-Tocotrienol suppresses VEGF induced angiogenesis whereas alpha-tocopherol does not. , 2009, Journal of agricultural and food chemistry.

[16]  Y. Yano,et al.  A redox-silent analogue of tocotrienol acts as a potential cytotoxic agent against human mesothelioma cells. , 2009, Life sciences.

[17]  K. Nakagawa,et al.  Antiangiogenic and anticancer potential of unsaturated vitamin E (tocotrienol). , 2009, The Journal of nutritional biochemistry.

[18]  D. Coppola,et al.  Vitamin E δ-Tocotrienol Levels in Tumor and Pancreatic Tissue of Mice after Oral Administration , 2009, Pharmacology.

[19]  Keith R Solomon,et al.  Cholesterol and Cholesterol-Rich Membranes in Prostate Cancer: An Update , 2008, Tumori.

[20]  Xìao-chun Xu,et al.  Statin Induces Apoptosis and Cell Growth Arrest in Prostate Cancer Cells , 2008, Cancer Epidemiology Biomarkers & Prevention.

[21]  H. Mukhtar,et al.  Chemoprevention of Prostate Cancer through Dietary Agents: Progress and Promise , 2007, Cancer Epidemiology Biomarkers & Prevention.

[22]  Karla A. Lawson,et al.  Supplemental and Dietary Vitamin E Intakes and Risk of Prostate Cancer in a Large Prospective Study , 2007, Cancer Epidemiology Biomarkers & Prevention.

[23]  H. Mo,et al.  Tocotrienols Potentiate Lovastatin-Mediated Growth Suppression In Vitro and In Vivo , 2007, Experimental biology and medicine.

[24]  Sanjay Gupta,et al.  Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptosis selectively in human prostate cancer cells. , 2006, Biochemical and biophysical research communications.

[25]  B. Ames,et al.  gamma-Tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[26]  A. Azzi,et al.  γ‐Tocopherol inhibits human cancer cell cycle progression and cell proliferation by down‐regulation of cyclins , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[27]  X. Lin,et al.  Modulation of docetaxel-induced apoptosis and cell cycle arrest by all- trans retinoic acid in prostate cancer cells , 2001, British Journal of Cancer.

[28]  E. Bruckheimer,et al.  Cell proliferation and apoptosis in prostate cancer: significance in disease progression and therapy. , 2000, Histology and histopathology.

[29]  P. Sylvester,et al.  Antiproliferative and Apoptotic Effects of Tocopherols and Tocotrienols on Preneoplastic and Neoplastic Mouse Mammary Epithelial Cells (44544) , 2000, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.