Tocotrienol Levels in Various Tissues of Sprague-Dawley Rats after Intragastric Administration of Tocotrienols

Okabe, Masaru; Oji, Mariko; Ikeda, Ikuo; Tachibana, Hirofumi; Yamada, Koji

doi:10.1271/bbb.66.1768

Cited by 38 publications

(25 citation statements)

References 8 publications

(10 reference statements)

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“…This study produced interesting results, as there was a significant 50-fold increase in the tocotrienol level in the adipose tissue compared with mice in the control group. This data confirmed previous study by Okabe et al (2002), on the accumulation and distribution of tocotrienols in diet. Furthermore, it was suggested that TRF showed antineoplastic activity by mimicking the effects of interferon-c based on the upregulation of certain genes responsible for the antiproliferative effects.…”

Section: In Vivo Studiessupporting

confidence: 93%

Tocotrienols and breast cancer: the evidence to date

et al. 2011

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Breast cancer is the second most frequent cancer affecting women worldwide after lung cancer. The toxicity factor associated with synthetic drugs has turned the attention toward natural compounds as the primary focus of interest as anticancer agents. Vitamin E derivatives consisting of the well-established tocopherols and their analogs namely tocotrienols have been extensively studied due to their remarkable biological properties. While tocopherols have failed to offer protection, tocotrienols, in particular, a-, d-, and c-tocotrienols alone and in combination have demonstrated anticancer properties. The discovery of the antiangiogenic, antiproliferative, and apoptotic effects of tocotrienols, as well as their role as an inducer of immunological functions, not only reveals a new horizon as a potent antitumor agent but also reinforces the notion that tocotrienols are indeed more than antioxidants. On the basis of a transcriptomic platform, we have recently demonstrated a novel mechanism for tocotrienol activity that involves estrogen receptor (ER) signaling. In silico simulations and in vitro binding analyses indicate a high affinity of specific forms of tocotrienols for ERb, but not for ERa. Moreover, we have demonstrated that specific tocotrienols increase ERb translocation into the nucleus which, in turn, activates the expression of estrogenresponsive genes (MIC-1, EGR-1 and Cathepsin D) in breast cancer cells only expressing ERb cells (MDA-MB-231) and in cells expressing both ER isoforms (MCF-7). The binding of specific tocotrienol forms to ERb is associated with the alteration of cell morphology, caspase-3 activation, DNA fragmentation, and apoptosis. Furthermore, a recently concluded clinical trial seems to suggest that tocotrienols in combination with tamoxifen may have the potential to extend breast cancer-specific survival.

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Section: In Vivo Studiessupporting

confidence: 93%

Tocotrienols and breast cancer: the evidence to date

et al. 2011

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“…Similarly, other studies had reported T3 deposition in various tissues of rats, especially in adipose tissues, skin and heart [24] . Taken together, this evidence suggests that T3 is absorbed in, and distributed efficiently to, various internal organs in vivo [24,25] . Nevertheless, the different levels of T3 deposition in the organs may be explained by several factors.…”

Section: Discussionsupporting

confidence: 64%

In vivo Evidence of γ-Tocotrienol as a Chemosensitizer in the Treatment of Hormone-Refractory Prostate Cancer

Yap¹,

Zaiden²,

Luk

et al. 2010

Pharmacology

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γ-Tocotrienol (γT3) is known to selectively kill prostate cancer (PCa) cells and to sensitize the cells to docetaxel (DTX)-induced apoptosis. In the present study, the pharmacokinetics of γT3 and the in vivo cytotoxic response of androgen-independent prostate cancer (AIPCa) tumor following γT3 treatment were investigated. Here, we investigated these antitumor effects for PCa tumors in vivo. The pharmacokinetic and tissue distribution of γT3 after exogenous γT3 supplementation were examined. Meanwhile, the response of the tumor to γT3 alone or in combination with DTX were studied by real-time in vivo bioluminescent imaging and by examination of biomarkers associated with cell proliferation and apoptosis. After intraperitoneal injection, γT3 rapidly disappeared from the serum and was selectively deposited in the AIPCa tumor cells. Administration of γT3 alone for 2 weeks resulted in a significant shrinkage of the AIPCa tumors. Meanwhile, further inhibition of the AIPCa tumor growth was achieved by combined treatment of γT3 and DTX (p < 0.002). The in vivo cytotoxic antitumor effects induced by γT3 seem to be associated with a decrease in expression of cell proliferation markers (proliferating cell nuclear antigen, Ki-67 and Id1) and an increase in the rate of cancer cell apoptosis [cleaved caspase 3 and poly(ADP-ribose) polymerase]. Additionally, the combined agents may be more effective at suppressing the invasiveness of AIPCa. Overall, our results indicate that γT3, either alone or in combination with DTX, may provide a treatment strategy that can improve therapeutic efficacy against AIPCa while reducing the toxicity often seen in patients treated with DTX.

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“…It is becoming clear that individual vitamin E forms possess different chemical and biological activities (6) and have distinct tissue distributions (46,47). We therefore hypothesize that combinations of different forms of vitamin E may be superior to each alone.…”

Section: Discussionmentioning

confidence: 96%

γ-Tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis

Jiang

Wong

Fyrst

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

184

147

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␥-Tocopherol (␥T), the predominant form of vitamin E in diets, but not ␣-tocopherol, the major vitamin E form in tissues and supplements, inhibits proliferation of prostate cancer cells (LNCaP and PC-3) and lung cancer cells (A549). In contrast, at similar concentrations, ␥T has no effect on normal prostate epithelial cells. Combinations of some vitamin E forms, such as ␥T and ␦-tocopherol, exhibit additive or synergistic inhibitory effects. In this study, ␥T or its combination with ␦-tocopherol induced apoptosis in androgen-sensitive prostate LNCaP, but not in androgenresistant PC-3 cells, by the induction of cytochrome c release, activation of caspase 9 and caspase 3, cleavage of poly-ADP-ribose polymerase (PARP), and involvement of caspase-independent pathways. Myriocin and fumonisin B1, specific inhibitors of key enzymes (serine palmitoyltransferase and dihydroceramide synthase, respectively) in de novo synthesis of sphingolipids, significantly protected cells from ␥T-induced DNA fragmentation, cytochrome c release, PARP cleavage, and the formation of active caspase 3. Compared with vehicle-treated controls, ␥T treatment led to pronounced dihydroceramide and dihydrosphingosine accumulation, which preceded morphological and biochemical manifestations of apoptosis. In contrast, ceramide and shpingosine levels did not increase until day 3, when substantial cell death took place. Our study demonstrates that ␥T and mixed vitamin E forms induce cell death by interrupting the de novo sphingolipid pathway in a prostate cancer cell line. Thus, certain vitamin E forms may be valuable as anticancer agents.

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Tocotrienol Levels in Various Tissues of Sprague-Dawley Rats after Intragastric Administration of Tocotrienols

Cited by 38 publications

References 8 publications

Tocotrienols and breast cancer: the evidence to date

Tocotrienols and breast cancer: the evidence to date

In vivo Evidence of γ-Tocotrienol as a Chemosensitizer in the Treatment of Hormone-Refractory Prostate Cancer

γ-Tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis

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