Synergistic Anticancer Effect of Tocotrienol Combined with Chemotherapeutic Agents or Dietary Components: A Review.
Tocotrienol (T3), unsaturated vitamin E, is gaining a lot of attention owing to its potent anticancer effect, since its efficacy is much greater than that of tocopherol (Toc). Various factors are known to be involved in such antitumor action, including cell cycle arrest, apoptosis induction, antiangiogenesis, anti-metastasis, nuclear factor-κB suppression, and telomerase inhibition. Owing to a difference in the affinity of T3 and Toc for the α-tocopherol transfer protein, the bioavailability of orally ingested T3 is lower than that of Toc. Furthermore, cellular uptake of T3 is interrupted by coadministration of α-Toc in vitro and in vivo. Based on this, several studies are in progress to screen for molecules that can synergize with T3 in order to augment its potency. Combinations of T3 with chemotherapeutic drugs (e.g., statins, celecoxib, and gefitinib) or dietary components (e.g., polyphenols, sesamin, and ferulic acid) exhibit synergistic actions on cancer cell growth and signaling pathways. In this review, we summarize the current status of synergistic effects of T3 and an array of agents on cancer cells, and discuss their molecular mechanisms of action. These combination strategies would encourage further investigation and application in cancer prevention and therapy.
Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan. eitsuka@nupals.ac.jp.
Takahiro
T
Eitsuka
Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan. tatewaki@nupals.ac.jp.
Naoto
N
Tatewaki
Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan. hnishida@nupals.ac.jp.
Hiroshi
H
Nishida
Food & Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan. nkgw@m.tohoku.ac.jp.
Kiyotaka
K
Nakagawa
Food and Biotechnology Innovation Project, New Industry Creation Hatchery Center (NICHe), Tohoku University, Sendai, Miyagi 980-8579, Japan. miyazawa@m.tohoku.ac.jp.|Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi 981-8555, Japan. miyazawa@m.tohoku.ac.jp.
Teruo
T
Miyazawa
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002392:Catechin / Q000031:analogs & derivatives / Q000627:therapeutic use; D003373:Coumaric Acids / Q000627:therapeutic use; D019587:Dietary Supplements; D004149:Dioxoles / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D017705:Lignans / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use; D024508:Tocotrienols / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D003373:Coumaric Acids; D004149:Dioxoles; D017705:Lignans; D013267:Stilbenes; D024508:Tocotrienols; D002392:Catechin; C004999:ferulic acid; C045651:epigallocatechin gallate; D000077185:Resveratrol; C054125:sesamin
cancer; synergy; tocotrienol; vitamin E
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