Synergistic anticancer effect of tocotrienol combined with chemotherapeutic agents or dietary components: A review

International Journal of Molecular Sciences

Volumn 17, Issue 10, 2016, Pages

  Eitsuka, Takahiro ^a   Tatewaki, Naoto ^a   Nishida, Hiroshi ^a   Nakagawa, Kiyotaka ^b   Miyazawa, Teruo ^b  

^a NIIGATA UNIVERSITY OF PHARMACY AND APPLIED LIFE SCIENCES   (Japan)

^b TOHOKU UNIVERSITY   (Japan)

Author keywords

Cancer; Synergy; Tocotrienol; Vitamin E

Indexed keywords

ALPHA TOCOPHEROL; ALPHA TOCOTRIENOL; CARRIER PROTEIN; CELECOXIB; EPIGALLOCATECHIN GALLATE; ERLOTINIB; FERULIC ACID; GEFITINIB; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; N (3 CHLOROPHENYL) 3 [3,5 DIMETHYL 4 (4 METHYL 1 PIPERAZINYLCARBONYL) 1H PYRROL 2 YLMETHYLENE] 2,3 DIHYDRO N METHYL 2 OXO 1H INDOLE 5 SULFONAMIDE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; RESVERATROL; SCATTER FACTOR; SESAMIN; TAMOXIFEN; TELOMERASE; 1,3 DIOXOLANE DERIVATIVE; ANTINEOPLASTIC AGENT; CATECHIN; COUMARIC ACID; LIGNAN; STILBENE DERIVATIVE;

ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; AUTOPHAGY; CANCER SURVIVAL; CELL GROWTH; CELL PROLIFERATION; CYTOTOXICITY; DIETARY INTAKE; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG POTENTIATION; GENE INACTIVATION; HUMAN; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; ANALOGS AND DERIVATIVES; COMBINATION DRUG THERAPY; DIETARY SUPPLEMENT; NEOPLASMS;

ANTINEOPLASTIC AGENTS; CATECHIN; COUMARIC ACIDS; DIETARY SUPPLEMENTS; DIOXOLES; DRUG SYNERGISM; DRUG THERAPY, COMBINATION; HUMANS; LIGNANS; NEOPLASMS; STILBENES; TOCOTRIENOLS;

EID: 85017085808     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms17101605     Document Type: Review

References (137)

1. Mustacich, D.J.; Bruno, R.S.; Traber, M.G. Vitamin E. Vitam. Horm. 2007, 76, 1-21
2. Packer, L.; Weber, S.U.; Rimbach, G. Molecular aspects of α-tocotrienol antioxidant action and cell signalling. J. Nutr. 2001, 131, 369S-373S
3. Pennock, J.F.; Hemming, F.W.; Kerr, J.D. A reassessment of tocopherol chemistry. Biochem. Biophys. Res. Commun. 1964, 17, 542-548
4. Qureshi, A.A.; Burger, W.C.; Peterson, D.M.; Elson, C.E. The structure of an inhibitor of cholesterol biosynthesis isolated from barley. J. Biol. Chem. 1986, 261, 10544-10550
5. Sundram, K.; Khor, H.T.; Ong, A.S.; Pathmanathan, R. Effect of dietary palm oils on mammary carcinogenesis in female rats induced by 7,12-dimethylbenz(a)anthracene. Cancer Res. 1989, 49, 1447-1451
6. Nesaretnam, K.; Guthrie, N.; Chambers, A.F.; Carroll, K.K. Effect of tocotrienols on the growth of a human breast cancer cell line in culture. Lipids 1995, 30, 1139-1143
7. Serbinova, E.; Kagan, V.; Han, D.; Packer, L. Free radical recycling and intramembrane mobility in the antioxidant properties of α-tocopherol and α-tocotrienol. Free Radic. Biol. Med. 1991, 10, 263-275
8. Wan Nazaimoon, W.M.; Khalid, B.A. Tocotrienols-rich diet decreases advanced glycosylation end-products in non-diabetic rats and improves glycemic control in streptozotocin-induced diabetic rats. Malays. J. Pathol. 2002, 24, 77-82
9. Wu, S.J.; Liu, P.L.; Ng, L.T. Tocotrienol-rich fraction of palm oil exhibits anti-inflammatory property by suppressing the expression of inflammatory mediators in human monocytic cells. Mol. Nutr. Food Res. 2008, 52, 921-929
10. Ren, Z.; Pae, M.; Dao, M.C.; Smith, D.; Meydani, S.N.; Wu, D. Dietary supplementation with tocotrienols enhances immune function in C57BL/6 mice. J. Nutr. 2010, 140, 1335-1341
11. Vasanthi, H.R.; Parameswari, R.P.; Das, D.K. Multifaceted role of tocotrienols in cardioprotection supports their structure: Function relation. Genes Nutr. 2012, 7, 19-28
12. Norazlina, M.; Lee, P.L.; Lukman, H.I.; Nazrun, A.S.; Ima-Nirwana, S. Effects of vitamin E supplementation on bone metabolism in nicotine-treated rats. Singap. Med. J. 2007, 48, 195-199.
13. Khanna, S.; Roy, S.; Slivka, A.; Craft, T.K.S.; Chaki, S.; Rink, C.; Notestine, M.A.; DeVries, A.C.; Parinandi, N.L.; Sen, C.K. Neuroprotective properties of the natural vitamin E α-tocotrienol. Stroke 2005, 36, 2258-2264
14. Ong, F.B.; Wan Ngah, W.Z.; Shamaan, N.A.; Md Top, A.G.; Marzuki, A.; Khalid, A.K. Glutathione S-transferase and γ-glutamyl transpeptidase activities in cultured rat hepatocytes treated with tocotrienol and tocopherol. Comp. Biochem. Physiol. C 1993, 106, 237-240
15. Gupta, A.; Chopra, K. Effect of tocotrienols on iron-induced renal dysfunction and oxidative stress in rats. Drug Chem. Toxicol. 2009, 32, 319-325
16. Suzuki, Y.J.; Tsuchiya, M.; Wassall, S.R.; Choo, Y.M.; Govil, G.; Kagan, V.E.; Packer, L. Structural and dynamic membrane properties of α-tocopherol and α-tocotrienol: Implication to the molecular mechanism of their antioxidant potency. Biochemistry 1993, 32, 10692-10699
17. Traber, M.G. Vitamin E regulatory mechanisms. Annu. Rev. Nutr. 2007, 27, 347-362
18. Hosomi, A.; Arita, M.; Sato, Y.; Kiyose, C.; Ueda, T.; Igarashi, O.; Arai, H.; Inoue, K. Affinity for α-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. FEBS Lett. 1997, 409, 105-108
19. O’Byrne, D.; Grundy, S.; Packer, L.; Devaraj, S.; Baldenius, K.; Hoppe, P.P.; Kraemer, K.; Jialal, I.; Traber, M.G. Studies of LDL oxidation following α-, γ-, or δ-tocotrienyl acetate supplementation of hypercholesterolemic humans. Free Radic. Biol. Med. 2000, 29, 834-845
20. Shibata, A.; Nakagawa, K.; Sookwong, P.; Tsuduki, T.; Asai, A.; Miyazawa, T. α-Tocopherol attenuates the cytotoxic effect of δ-tocotrienol in human colorectal adenocarcinoma cells. Biochem. Biophys. Res. Commun. 2010, 397, 214-219
21. Ikeda, S.; Tohyama, T.; Yoshimura, H.; Hamamura, K.; Abe, K.; Yamashita, K. Dietary α-tocopherol decreases α-tocotrienol but not γ-tocotrienol concentration in rats. J. Nutr. 2003, 133, 428-434
22. Mo, H.; Elson, C.E. Studies of the isoprenoid-mediated inhibition of mevalonate synthesis applied to cancer chemotherapy and chemoprevention. Exp. Biol. Med. 2004, 229, 567-585.
23. Bachawal, S.V.; Wali, V.B.; Sylvester, P.W. Enhanced antiproliferative and apoptotic response to combined treatment of γ-tocotrienol with erlotinib or gefitinib in mammary tumor cells. BMC Cancer 2010
24. Shirode, A.B.; Sylvester, P.W. Synergistic anticancer effects of combined γ-tocotrienol and celecoxib treatment are associated with suppression in Akt and NFκB signaling. Biomed. Pharmacother. 2010, 64, 327-332
25. Ayoub, N.M.; Bachawal, S.V.; Sylvester, P.W. γ-Tocotrienol inhibits HGF-dependent mitogenesis and Met activation in highly malignant mammary tumour cells. Cell Prolif. 2011, 44, 516-526
26. Malaviya, A.; Sylvester, P.W. Mechanisms mediating the effects of γ-tocotrienol when used in combination with PPARγ agonists or antagonists on MCF-7 and MDA-MB-231 breast cancer cells. Int. J. Breast Cancer 2013, 2013, 101705
27. Tiwari, R.V.; Parajuli, P.; Sylvester, P.W. Synergistic anticancer effects of combined γ-tocotrienol and oridonin treatment is associated with the induction of autophagy. Mol. Cell. Biochem. 2015, 408, 123-137
28. Yamashita, S.; Baba, K.; Makio, A.; Kumazoe, M.; Huang, Y.; Lin, I.C.; Bae, J.; Murata, M.; Yamada, S.; Tachibana, H. γ-Tocotrienol upregulates aryl hydrocarbon receptor expression and enhances the anticancer effect of baicalein. Biochem. Biophys. Res. Commun. 2016, 473, 801-807
29. Hsieh, T.C.; Wu, J.M. Suppression of cell proliferation and gene expression by combinatorial synergy of EGCG, resveratrol and γ-tocotrienol in estrogen receptor-positive MCF-7 breast cancer cells. Int. J. Oncol. 2008, 33, 851-859
30. Akl, M.R.; Ayoub, N.M.; Sylvester, P.W. Mechanisms mediating the synergistic anticancer effects of combined γ-tocotrienol and sesamin treatment. Planta Med. 2012, 78, 1731-1739
31. Eitsuka, T.; Tatewaki, N.; Nishida, H.; Kurata, T.; Nakagawa, K.; Miyazawa, T. Synergistic inhibition of cancer cell proliferation with a combination of δ-tocotrienol and ferulic acid. Biochem. Biophys. Res. Commun. 2014, 453, 606-611
32. Goldstein, J.L.; Brown, M.S. Regulation of the mevalonate pathway. Nature 1990, 343, 425-430
33. Zhang, F.L.; Casey, P.J. Protein prenylation: Molecular mechanisms and functional consequences. Annu. Rev. Biochem. 1996, 65, 241-269
34. Dricu, A.; Carlberg, M.; Wang, M.; Larsson, O. Inhibition of N-linked glycosylation using tunicamycin causes cell death in malignant cells: Role of down-regulation of the insulin-like growth factor 1 receptor in induction of apoptosis. Cancer Res. 1997, 57, 543-548
35. Demierre, M.F.; Higgins, P.D.; Gruber, S.B.; Hawk, E.; Lippman, S.M. Statins and cancer prevention. Nat. Rev. Cancer 2005, 5, 930-942
36. Parker, R.A.; Pearce, B.C.; Clark, R.W.; Gordon, D.A.; Wright, J.J. Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J. Biol. Chem. 1993, 268, 11230-11238
37. Song, B.L.; DeBose-Boyd, R.A. Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by δ- and γ-tocotrienols. J. Biol. Chem. 2006, 281, 25054-25061
38. Hussein, D.; Mo, H. d-δ-Tocotrienol-mediated suppression of the proliferation of human PANC-1, MIA PaCa-2, and BxPC-3 pancreatic carcinoma cells. Pancreas 2009, 38, e124-e136
39. McAnally, J.A.; Gupta, J.; Sodhani, S.; Bravo, L.; Mo, H. Tocotrienols potentiate lovastatin-mediated growth suppression in vitro and in vivo. Exp. Biol. Med. 2007, 232, 523-531.
40. Wali, V.B.; Sylvester, P.W. Synergistic antiproliferative effects of γ-tocotrienol and statin treatment on mammary tumor cells. Lipids 2007, 42, 1113-1123
41. Yang, Z.; Xiao, H.; Jin, H.; Koo, P.T.; Tsang, D.J.; Yang, C.S. Synergistic actions of atorvastatin with γ-tocotrienol and celecoxib against human colon cancer HT29 and HCT116 cells. Int. J. Cancer 2010, 126, 852-863
42. Fernandes, N.V.; Guntipalli, P.K.; Mo, H. d-δ-Tocotrienol-mediated cell cycle arrest and apoptosis in human melanoma cells. Anticancer Res. 2010, 30, 4937-4944
43. Yuan, Y.; Li, X.F.; Chen, J.Q.; Dong, C.X.; Weng, S.S.; Huang, J.J. Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer. OncoTargets Ther. 2014, 7, 841-852
44. Ciardiello, F.; Tortora, G. EGFR antagonists in cancer treatment. N. Engl. J. Med. 2008, 358, 1160-1174
45. Hynes, N.E.; Lane, H.A. ERBB receptors and cancer: The complexity of targeted inhibitors. Nat. Rev. Cancer 2005, 5, 341-354
46. Laurent-Puig, P.; Lievre, A.; Blons, H. Mutations and response to epidermal growth factor receptor inhibitors. Clin. Cancer Res. 2009, 15, 1133-1139
47. Olayioye, M.A.; Neve, R.M.; Lane, H.A.; Hynes, N.E. The ErbB signaling network: Receptor heterodimerization in development and cancer. EMBO J. 2000, 19, 3159-3167
48. Samant, G.V.; Sylvester, P.W. γ-Tocotrienol inhibits ErbB3-dependent PI3K/Akt mitogenic signalling in neoplastic mammary epithelial cells. Cell Prolif. 2006, 39, 563-574
49. Shin-Kang, S.; Ramsauer, V.P.; Lightner, J.; Chakraborty, K.; Stone, W.; Campbell, S.; Reddy, S.A.; Krishnan, K. Tocotrienols inhibit AKT and ERK activation and suppress pancreatic cancer cell proliferation by suppressing the ErbB2 pathway. Free Radic. Biol. Med. 2011, 51, 1164-1174
50. Pierpaoli, E.; Viola, V.; Barucca, A.; Orlando, F.; Galli, F.; Provinciali, M. Effect of annatto-tocotrienols supplementation on the development of mammary tumors in HER-2/neu transgenic mice. Carcinogenesis 2013, 34, 1352-1360
51. Alawin, O.A.; Ahmed, R.A.; Ibrahim, B.A.; Briski, K.P.; Sylvester, P.W. Antiproliferative effects of γ-tocotrienol are associated with lipid raft disruption in HER2-positive human breast cancer cells. J. Nutr. Biochem. 2016, 27, 266-277
52. Bachawal, S.V.; Wali, V.B.; Sylvester, P.W. Combined γ-tocotrienol and erlotinib/gefitinib treatment suppresses Stat and Akt signaling in murine mammary tumor cells. Anticancer Res. 2010, 30, 429-437
53. Thun, M.J.; Henley, S.J.; Patrono, C. Nonsteroidal anti-inflammatory drugs as anticancer agents: Mechanistic, pharmacologic, and clinical issues. J. Natl. Cancer Inst. 2002, 94, 252-266
54. Brown, J.R.; DuBois, R.N. Cyclooxygenase as a target in lung cancer. Clin. Cancer Res. 2004, 10, 4266s-4269s
55. Pai, R.; Soreghan, B.; Szabo, I.L.; Pavelka, M.; Baatar, D.; Tarnawski, A.S. Prostaglandin E2 transactivates EGF receptor: A novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat. Med. 2002, 8, 289-293
56. Shostak, K.; Chariot, A. EGFR and NF-κB: Partners in cancer. Trends Mol. Med. 2015, 21, 385-393
57. Ozes, O.N.; Mayo, L.D.; Gustin, J.A.; Pfeffer, S.R.; Pfeffer, L.M.; Donner, D.B. NF-κB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature 1999, 401, 82-85
58. Gupta, S.C.; Sundaram, C.; Reuter, S.; Aggarwal, B.B. Inhibiting NF-κB activation by small molecules as a therapeutic strategy. Biochim. Biophys. Acta 2010, 1799, 775-787
59. Shishodia, S.; Koul, D.; Aggarwal, B.B. Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates TNF-induced NF-κB activation through inhibition of activation of IκB α kinase and Akt in human non-small cell lung carcinoma: Correlation with suppression of COX-2 synthesis. J. Immunol. 2004, 173, 2011-2022
60. Shah, S.J.; Sylvester, P.W. Γ-tocotrienol inhibits neoplastic mammary epithelial cell proliferation by decreasing Akt and nuclear factor κB activity. Exp. Biol. Med. 2005, 230, 235-241.
61. Ahn, K.S.; Sethi, G.; Krishnan, K.; Aggarwal, B.B. Γ-tocotrienol inhibits nuclear factor-κB signaling pathway through inhibition of receptor-interacting protein and TAK1 leading to suppression of antiapoptotic gene products and potentiation of apoptosis. J. Biol. Chem. 2007, 282, 809-820
62. Yap, W.N.; Chang, P.N.; Han, H.Y.; Lee, D.T.; Ling, M.T.; Wong, Y.C.; Yap, Y.L. Γ-tocotrienol suppresses prostate cancer cell proliferation and invasion through multiple-signalling pathways. Br. J. Cancer 2008, 99, 1832-1841
63. Xu, W.L.; Liu, J.R.; Liu, H.K.; Qi, G.Y.; Sun, X.R.; Sun, W.G.; Chen, B.Q. Inhibition of proliferation and induction of apoptosis by γ-tocotrienol in human colon carcinoma HT-29 cells. Nutrition 2009, 25, 555-566
64. Chang, P.N.; Yap, W.N.; Lee, D.T.; Ling, M.T.; Wong, Y.C.; Yap, Y.L. Evidence of γ-tocotrienol as an apoptosis-inducing, invasion-suppressing, and chemotherapy drug-sensitizing agent in human melanoma cells. Nutr. Cancer 2009, 61, 357-366
65. Yap, W.N.; Zaiden, N.; Tan, Y.L.; Ngoh, C.P.; Zhang, X.W.; Wong, Y.C.; Ling, M.T.; Yap, Y.L. Id1, inhibitor of differentiation, is a key protein mediating anti-tumor responses of γ-tocotrienol in breast cancer cells. Cancer Lett. 2010, 291, 187-199
66. Kunnumakkara, A.B.; Sung, B.; Ravindran, J.; Diagaradjane, P.; Deorukhkar, A.; Dey, S.; Koca, C.; Yadav, V.R.; Tong, Z.; Gelovani, J.G.; et al. Γ-tocotrienol inhibits pancreatic tumors and sensitizes them to gemcitabine treatment by modulating the inflammatory microenvironment. Cancer Res. 2010, 70, 8695-8705
67. Ji, X.; Wang, Z.; Geamanu, A.; Sarkar, F.H.; Gupta, S.V. Inhibition of cell growth and induction of apoptosis in non-small cell lung cancer cells by δ-tocotrienol is associated with notch-1 down-regulation. J. Cell. Biochem. 2011, 112, 2773-2783
68. Manu, K.A.; Shanmugam, M.K.; Ramachandran, L.; Li, F.; Fong, C.W.; Kumar, A.P.; Tan, P.; Sethi, G. First evidence that γ-tocotrienol inhibits the growth of human gastric cancer and chemosensitizes it to capecitabine in a xenograft mouse model through the modulation of NF-κB pathway. Clin. Cancer Res. 2012, 18, 2220-2229
69. Kani, K.; Momota, Y.; Harada, M.; Yamamura, Y.; Aota, K.; Yamanoi, T.; Takano, H.; Motegi, K.; Azuma, M. γ-Tocotrienol enhances the chemosensitivity of human oral cancer cells to docetaxel through the downregulation of the expression of NF-κB-regulated anti-apoptotic gene products. Int. J. Oncol. 2013, 42, 75-82
70. Wang, Y.; Park, N.Y.; Jang, Y.; Ma, A.; Jiang, Q. Vitamin E γ-tocotrienol inhibits cytokine-stimulated NF-κB activation by induction of anti-inflammatory A20 via stress adaptive response due to modulation of sphingolipids. J. Immunol. 2015, 195, 126-133
71. Shirode, A.B.; Sylvester, P.W. Mechanisms mediating the synergistic anticancer effects of combined γ-tocotrienol and celecoxib treatment. J. Bioanal. Biomed. 2011, 3, 1-7
72. Bottaro, D.P.; Rubin, J.S.; Faletto, D.L.; Chan, A.M.; Kmiecik, T.E.; Vande Woude, G.F.; Aaronson, S.A. Identification of the hepatocyte growth factor receptor as the c-Met proto-oncogene product. Science 1991, 251, 802-804
73. Eder, J.P.; Vande Woude, G.F.; Boerner, S.A.; LoRusso, P.M. Novel therapeutic inhibitors of the c-Met signaling pathway in cancer. Clin. Cancer Res. 2009, 15, 2207-2214
74. Guo, A.; Villén, J.; Kornhauser, J.; Lee, K.A.; Stokes, M.P.; Rikova, K.; Possemato, A.; Nardone, J.; Innocenti, G.; Wetzel, R.; et al. Signaling networks assembled by oncogenic EGFR and c-Met. Proc. Natl. Acad. Sci. USA 2008, 105, 692-697
75. Ayoub, N.M.; Akl, M.R.; Sylvester, P.W. Combined γ-tocotrienol and Met inhibitor treatment suppresses mammary cancer cell proliferation, epithelial-to-mesenchymal transition and migration. Cell Prolif. 2013, 46, 538-553
76. Mangelsdorf, D.J.; Evans, R.M. The RXR heterodimers and orphan receptors. Cell 1995, 83, 841-850
77. Koeffler, H.P. Peroxisome proliferator-activated receptor γ and cancers. Clin. Cancer Res. 2003, 9, 1-9
78. Ricote, M.; Li, A.C.; Willson, T.M.; Kelly, C.J.; Glass, C.K. The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature 1998, 391, 79-82
79. Campbell, S.E.; Rudder, B.; Phillips, R.B.; Whaley, S.G.; Stimmel, J.B.; Leesnitzer, L.M.; Lightner, J.; Dessus-Babus, S.; Duffourc, M.; Stone, W.L.; et al. γ-Tocotrienol induces growth arrest through a novel pathway with TGFβ2 in prostate cancer. Free Radic. Biol. Med. 2011, 50, 1344-1354
80. Malaviya, A.; Sylvester, P.W. Synergistic antiproliferative effects of combined γ-tocotrienol and PPARγ antagonist treatment are mediated through PPAR γ-independent mechanisms in breast cancer cells. PPAR Res. 2014, 2014, 439146
81. Rabinowitz, J.D.; White, E. Autophagy and metabolism. Science 2010, 330, 1344-1348
82. Lin, L.; Baehrecke, E.H. Autophagy, cell death, and cancer. Mol. Cell. Oncol. 2015, 2, e985913
83. Su, Z.; Yang, Z.; Xu, Y.; Chen, Y.; Yu, Q. Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol. Cancer 2015, 14, 48
84. Jiang, Q.; Rao, X.; Kim, C.Y.; Freiser, H.; Zhang, Q.; Jiang, Z.; Li, G. γ-Tocotrienol induces apoptosis and autophagy in prostate cancer cells by increasing intracellular dihydrosphingosine and dihydroceramide. Int. J. Cancer 2012, 130, 685-693
85. Tiwari, R.V.; Parajuli, P.; Sylvester, P.W. γ-Tocotrienol-induced autophagy in malignant mammary cancer cells. Exp. Biol. Med. 2014, 239, 33-44
86. Cui, Q.; Tashiro, S.; Onodera, S.; Minami, M.; Ikejima, T. Autophagy preceded apoptosis in oridonin-treated human breast cancer MCF-7 cells. Biol. Pharm. Bull. 2007, 30, 859-864
87. Safe, S.; Lee, S.O.; Jin, U.H. Role of the aryl hydrocarbon receptor in carcinogenesis and potential as a drug target. Toxicol. Sci. 2013, 135, 1-16
88. Pang, P.H.; Lin, Y.H.; Lee, Y.H.; Hou, H.H.; Hsu, S.P.; Juan, S.H. Molecular mechanisms of p21 and p27 induction by 3-methylcholanthrene, an aryl-hydrocarbon receptor agonist, involved in antiproliferation of human umbilical vascular endothelial cells. J. Cell. Physiol. 2008, 215, 161-171
89. Matikainen, T.; Perez, G.I.; Jurisicova, A.; Pru, J.K.; Schlezinger, J.J.; Ryu, H.Y.; Laine, J.; Sakai, T.; Korsmeyer, S.J.; Casper, R.F.; et al. Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals. Nat. Genet. 2001, 28, 355-360
90. Contador-Troca, M.; Alvarez-Barrientos, A.; Barrasa, E.; Rico-Leo, E.M.; Catalina-Fernández, I.; Menacho-Márquez, M.; Bustelo, X.R.; García-Borrón, J.C.; Gómez-Durán, A.; Sáenz-Santamaría, J.; et al. The dioxin receptor has tumor suppressor activity in melanoma growth and metastasis. Carcinogenesis 2013, 34, 2683-2693
91. Cheng, Y.H.; Li, L.A.; Lin, P.; Cheng, L.C.; Hung, C.H.; Chang, N.W.; Lin, C. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation. Toxicol. Appl. Pharmacol. 2012, 263, 360-367
92. Manach, C.; Scalbert, A.; Morand, C.; Remesy, C.; Jimenez, L. Polyphenols: Food sources and bioavailability. Am. J. Clin. Nutr. 2004, 79, 727-747
93. Burns, J.; Yokota, T.; Ashihara, H.; Lean, M.E.; Crozier, A. Plant foods and herbal sources of resveratrol. J. Agric. Food Chem. 2002, 50, 3337-3340
94. Singh, B.N.; Shankar, S.; Srivastava, R.K. Green tea catechin, epigallocatechin-3-gallate (EGCG): Mechanisms, perspectives and clinical applications. Biochem. Pharmacol. 2011, 82, 1807-1821
95. Singh, C.K.; Ndiaye, M.A.; Ahmad, N. Resveratrol and cancer: Challenges for clinical translation. Biochim. Biophys. Acta 2015, 1852, 1178-1185
96. Shimizu, M.; Shirakami, Y.; Moriwaki, H. Targeting receptor tyrosine kinases for chemoprevention by green tea catechin, EGCG. Int. J. Mol. Sci. 2008, 9, 1034-1049
97. Provinciali, M.; Re, F.; Donnini, A.; Orlando, F.; Bartozzi, B.; di Stasio, G.; Smorlesi, A. Effect of resveratrol on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Int. J. Cancer 2005, 115, 36-45
98. Cho, I.J.; Ahn, J.Y.; Kim, S.; Choi, M.S.; Ha, T.Y. Resveratrol attenuates the expression of HMG-CoA reductase mRNA in hamsters. Biochem. Biophys. Res. Commun. 2008, 367, 190-194
99. Wong, D.H.; Villanueva, J.A.; Cress, A.B.; Sokalska, A.; Ortega, I.; Duleba, A.J. Resveratrol inhibits the mevalonate pathway and potentiates the antiproliferative effects of simvastatin in rat theca-interstitial cells. Fertil. Steril. 2011, 96, 1252-1258
100. Dinkova-Kostova, A.T.; Talalay, P. NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a multifunctional antioxidant enzyme and exceptionally versatile cytoprotector. Arch. Biochem. Biophys. 2010, 501, 116-123
101. Kensler, T.W.; Wakabayashi, N. Nrf2: Friend or foe for chemoprevention? Carcinogenesis 2010, 31, 90-99
102. Sriram, N.; Kalayarasan, S.; Sudhandiran, G. Epigallocatechin-3-gallate augments antioxidant activities and inhibits inflammation during bleomycin-induced experimental pulmonary fibrosis through Nrf2-Keap1 signaling. Pulm. Pharmacol. Ther. 2009, 22, 221-236
103. Hsieh, T.C.; Lu, X.; Wang, Z.; Wu, J.M. Induction of quinone reductase NQO1 by resveratrol in human K562 cells involves the antioxidant response element ARE and is accompanied by nuclear translocation of transcription factor Nrf2. Med. Chem. 2006, 2, 275-285
104. Hsieh, T.C.; Elangovan, S.; Wu, J.M. Differential suppression of proliferation in MCF-7 and MDA-MB-231 breast cancer cells exposed to α-, γ- and delta-tocotrienols is accompanied by altered expression of oxidative stress modulatory enzymes. Anticancer Res. 2010, 30, 4169-4176
105. Cao, J.; Chen, J.; Xie, L.; Wang, J.; Feng, C.; Song, J. Protective properties of sesamin against fluoride-induced oxidative stress and apoptosis in kidney of carp (Cyprinus carpio) via JNK signaling pathway. Aquat. Toxicol. 2015, 167, 180-190
106. Shimizu, S.; Akimoto, K.; Shinmen, Y.; Kawashima, H.; Sugano, M.; Yamada, H. Sesamin is a potent and specific inhibitor of δ5 desaturase in polyunsaturated fatty acid biosynthesis. Lipids 1991, 26, 512-516
107. Hirose, N.; Inoue, T.; Nishihara, K.; Sugano, M.; Akimoto, K.; Shimizu, S.; Yamada, H. Inhibition of cholesterol absorption and synthesis in rats by sesamin. J. Lipid Res. 1991, 32, 629-638
108. Nakano, D.; Itoh, C.; Ishii, F.; Kawanishi, H.; Takaoka, M.; Kiso, Y.; Tsuruoka, N.; Tanaka, T.; Matsumura, Y. Effects of sesamin on aortic oxidative stress and endothelial dysfunction in deoxycorticosterone acetate-salt hypertensive rats. Biol. Pharm. Bull. 2003, 26, 1701-1705
109. Fujikawa, T.; Kanada, N.; Shimada, A.; Ogata, M.; Suzuki, I.; Hayashi, I.; Nakashima, K. Effect of sesamin in Acanthopanax senticosus HARMS on behavioral dysfunction in rotenone-induced parkinsonian rats. Biol. Pharm. Bull. 2005, 28, 169-172
110. Yokota, T.; Matsuzaki, Y.; Koyama, M.; Hitomi, T.; Kawanaka, M.; Enoki-Konishi, M.; Okuyama, Y.; Takayasu, J.; Nishino, H.; Nishikawa, A.; et al. Sesamin, a lignan of sesame, down-regulates cyclin D1 protein expression in human tumor cells. Cancer Sci. 2007, 98, 1447-1453
111. Monteiro, E.M.; Chibli, L.A.; Yamamoto, C.H.; Pereira, M.C.; Vilela, F.M.; Rodarte, M.P.; Pinto, M.A.; do Amaral Mda, P.; Silverio, M.S.; Araujo, A.L.; et al. Antinociceptive and anti-inflammatory activities of the sesame oil and sesamin. Nutrients 2014, 6, 1931-1944
112. You, C.S.; Sontag, T.J.; Swanson, J.E.; Parker, R.S. Long-chain carboxychromanols are the major metabolites of tocopherols and tocotrienols in A549 lung epithelial cells but not HepG2 cells. J. Nutr. 2005, 135, 227-232
113. Ikeda, S.; Toyoshima, K.; Yamashita, K. Dietary sesame seeds elevate α- and γ-tocotrienol concentrations in skin and adipose tissue of rats fed the tocotrienol-rich fraction extracted from palm oil. J. Nutr. 2001, 131, 2892-2897
114. Sontag, T.J.; Parker, R.S. Cytochrome P450 ω-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. J. Biol. Chem. 2002, 277, 25290-25296
115. Parker, R.S.; Sontag, T.J.; Swanson, J.E. Cytochrome P4503A-dependent metabolism of tocopherols and inhibition by sesamin. Biochem. Biophys. Res. Commun. 2000, 277, 531-534
116. Birringer, M.; Pfluger, P.; Kluth, D.; Landes, N.; Brigelius-Flohé, R. Identities and differences in the metabolism of tocotrienols and tocopherols in HepG2 cells. J. Nutr. 2002, 132, 3113-3118
117. Freiser, H.; Jiang, Q. Γ-tocotrienol and γ-tocopherol are primarily metabolized to conjugated 2-(β-carboxyethyl)-6-hydroxy-2,7,8-trimethylchroman and sulfated long-chain carboxychromanols in rats. J. Nutr. 2009, 139, 884-889
118. Abe, C.; Uchida, T.; Ohta, M.; Ichikawa, T.; Yamashita, K.; Ikeda, S. Cytochrome P450-dependent metabolism of vitamin E isoforms is a critical determinant of their tissue concentrations in rats. Lipids 2007, 42, 637-645
119. Akl, M.R.; Ayoub, N.M.; Abuasal, B.S.; Kaddoumi, A.; Sylvester, P.W. Sesamin synergistically potentiates the anticancer effects of γ-tocotrienol in mammary cancer cell lines. Fitoterapia 2013, 84, 347-359
120. Henderson, A.J.; Ollila, C.A.; Kumar, A.; Borresen, E.C.; Raina, K.; Agarwal, R.; Ryan, E.P. Chemopreventive properties of dietary rice bran: Current status and future prospects. Adv. Nutr. 2012, 3, 643-653
121. Tantamango, Y.M.; Knutsen, S.F.; Beeson, W.L.; Fraser, G.; Sabate, J. Foods and food groups associated with the incidence of colorectal polyps: The Adventist Health Study. Nutr. Cancer 2011, 63, 565-572
122. Miyazawa, T.; Shibata, A.; Sookwong, P.; Kawakami, Y.; Eitsuka, T.; Asai, A.; Oikawa, S.; Nakagawa, K. Antiangiogenic and anticancer potential of unsaturated vitamin E (tocotrienol): A review. J. Nutr. Biochem. 2009, 20, 79-86
123. Eitsuka, T.; Nakagawa, K.; Miyazawa, T. Down-regulation of telomerase activity in DLD-1 human colorectal adenocarcinoma cells by tocotrienol. Biochem. Biophys. Res. Commun. 2006, 348, 170-175
124. Kawabata, K.; Yamamoto, T.; Hara, A.; Shimizu, M.; Yamada, Y.; Matsunaga, K.; Tanaka, T.; Mori, H. Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in F344 rats. Cancer Lett. 2000, 157, 15-21
125. Ohnishi, M.; Matuo, T.; Tsuno, T.; Hosoda, A.; Nomura, E.; Taniguchi, H.; Sasaki, H.; Morishita, H. Antioxidant activity and hypoglycemic effect of ferulic acid in STZ-induced diabetic mice and KK-Ay mice. Biofactors 2004, 21, 315-319
126. Xu, X.; Xiao, H.; Zhao, J.; Zhao, T. Cardioprotective effect of sodium ferulate in diabetic rats. Int. J. Med. Sci. 2012, 9, 291-300
127. Yan, J.J.; Cho, J.Y.; Kim, H.S.; Kim, K.L.; Jung, J.S.; Huh, S.O.; Suh, H.W.; Kim, Y.H.; Song, D.K. Protection against beta-amyloid peptide toxicity in vivo with long-term administration of ferulic acid. Br. J. Pharmacol. 2001, 133, 89-96
128. Zhao, Z.; Egashira, Y.; Sanada, H. Ferulic acid sugar esters are recovered in rat plasma and urine mainly as the sulfoglucuronide of ferulic acid. J. Nutr. 2003, 133, 1355-1361
129. Eitsuka, T.; Tatewaki, N.; Nishida, H.; Nakagawa, K.; Miyazawa, T. A combination of δ-tocotrienol and ferulic acid synergistically inhibits telomerase activity in DLD-1 human colorectal adenocarcinoma cells. J. Nutr. Sci. Vitaminol. 2016, 62, 281-287.
130. Sookwong, P.; Nakagawa, K.; Yamaguchi, Y.; Miyazawa, T.; Kato, S.; Kimura, F.; Miyazawa, T. Tocotrienol distribution in foods: Estimation of daily tocotrienol intake of Japanese population. J. Agric. Food Chem. 2010, 58, 3350-3355
131. Hiura, Y.; Tachibana, H.; Arakawa, R.; Aoyama, N.; Okabe, M.; Sakai, M.; Yamada, K. Specific accumulation of γ- and δ-tocotrienols in tumor and their antitumor effect in vivo. Nutr. Biochem. 2009, 20, 607-613
132. Yap, S.P.; Yuen, K.H.; Wong, J.W. Pharmacokinetics and bioavailability of α-, γ- and δ-tocotrienols under different food status. J. Pharm. Pharmacol. 2001, 53, 67-71
133. Nesaretnam, K.; Selvaduray, K.R.; Abdul Razak, G.; Veerasenan, S.D.; Gomez, P.A. Effectiveness of tocotrienol-rich fraction combined with tamoxifen in the management of women with early breast cancer: A pilot clinical trial. Breast Cancer Res. 2010, 12, R81
134. Rice, S.; Whitehead, S.A. Phytoestrogens oestrogen synthesis and breast cancer. J. Steroid Biochem. Mol. Biol. 2008, 108, 186-195
135. Lindberg, K.; Helguero, L.A.; Omoto, Y.; Gustafsson, J.Å.; Haldosén, L.A. Estrogen receptor β represses Akt signaling in breast cancer cells via downregulation of HER2/HER3 and upregulation of PTEN: Implications for tamoxifen sensitivity. Breast Cancer Res. 2011, 13, R43
136. Comitato, R.; Nesaretnam, K.; Leoni, G.; Ambra, R.; Canali, R.; Bolli, A.; Marino, M.; Virgili, F. A novel mechanism of natural vitamin E tocotrienol activity: Involvement of ERβ signal transduction. Am. J. Physiol. Endocrinol. Metab. 2009, 297, E427-E437
137. Comitato, R.; Leoni, G.; Canali, R.; Ambra, R.; Nesaretnam, K.; Virgili, F. Tocotrienols activity in MCF-7 breast cancer cells: Involvement of ERβ signal transduction. Mol. Nutr. Food Res. 2010, 54, 669-678