The effect of α- and γ-tocopherol and their carboxyethyl hydroxychroman metabolites on prostate cancer cell proliferation

Galli, Francesco; Stabile, Anna Maria; Betti, Michele; Conte, Carmela; Pistilli, Alessandra; Rende, Mario; Floridi, Ardesio; Azzi, Angelo

doi:10.1016/j.abb.2003.11.014

Cited by 106 publications

(97 citation statements)

References 25 publications

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“…Furthermore, our results showing that ␥-tocotrienol suppresses NF-B-regulated COX-2 and ICAM-1 expression are in agreement with a previous report involving human neoplastic mammary epithelial cells and human umbilical vein endothelial cells (27,29). Similarly, our findings that ␥-tocotrienol down-regulates cyclin D1 expression are in agreement with previous reports (14) that showed that down-regulation of cyclin D1 is responsible for cell cycle arrest at the G 0 /G 1 phase. Our report, however, is the first to show that ␥-tocotrienol suppresses TNF-induced MMP-9 expression, which plays a crucial role in tumor invasion and angiogenesis by mediating the degradation of the extracellular matrix (91).…”

Section: Discussionsupporting

confidence: 82%

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

Ahn

Sethi

Krishnan

et al. 2007

Journal of Biological Chemistry

234

205

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Unlike the tocopherols, the tocotrienols, also members of the vitamin E family, have an unsaturated isoprenoid side chain. In contrast to extensive studies on tocopherol, very little is known about tocotrienol. Because the nuclear factor-B (NF-B) pathway has a central role in tumorigenesis, we investigated the effect of ␥-tocotrienol on the NF-B pathway. Although ␥-tocotrienol completely abolished tumor necrosis factor ␣ (TNF)-induced NF-B activation, a similar dose of ␥-tocopherol had no effect. Besides TNF, ␥-tocotrienol also abolished NF-B activation induced by phorbol myristate acetate, okadaic acid, lipopolysaccharide, cigarette smoke, interleukin-1␤, and epidermal growth factor. Constitutive NF-B activation expressed by certain tumor cells was also abrogated by ␥-tocotrienol. Reducing agent had no effect on the ␥-tocotrienol-

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Section: Discussionsupporting

confidence: 82%

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

Ahn

Sethi

Krishnan

et al. 2007

Journal of Biological Chemistry

234

205

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“…In the same study, significant protective effects of high concentrations of selenium and ␣T were observed only when ␥T concentrations were high. Consistently, ␥T and its metabolite, 2,7,8-trimethyl-2-(␤-carboxyethyl)-6-hydroxychroman, is more potent than ␣T in inhibiting prostate cancer cell growth by the down-regulation of cyclins (14,15). ␥T is also stronger than ␣T in the induction of peroxisome proliferatoractivated receptor-␥ in colon cancer cell lines (16).…”

mentioning

confidence: 54%

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.

186

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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“…The unique gene regulatory properties of a-tocopherol suggest the existence of a receptor, but, despite intensive search, such a protein has not been identified (7,8). An attempt has also been made to identify active metabolites, possibly involved in a-tocopherol signaling functions (9).…”

mentioning

confidence: 99%

On the Existence of Cellular Tocopheryl Phosphate, its Synthesis, Degradation and Cellular Roles: A Hypothesis

Negis

Zingg

Ogru³

et al. 2005

IUBMB Life (International Union of Biochemistry and Molecular B

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The finding that a-tocopheryl phosphate is present in cells in small amounts, that it can be synthesized and hydrolyzed supports the hypothesis that a-tocopheryl phosphate might be a signaling molecule. The possible pathways needed for the synthesis, hydrolysis and signaling are considered in this hypothesis as well the possible extension of this reaction to additional molecules such as tocopherols and tocotrienols. A possible mechanism of action of other tocopherol esters (succinate and maleate) is also hypothesized.

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The effect of α- and γ-tocopherol and their carboxyethyl hydroxychroman metabolites on prostate cancer cell proliferation

Cited by 106 publications

References 25 publications

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

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

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

On the Existence of Cellular Tocopheryl Phosphate, its Synthesis, Degradation and Cellular Roles: A Hypothesis

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