Vitamin E and other antioxidants inhibit human prostate cancer cells through apoptosis

Gunawardena, Kushlani; Murray, Darrell K.; Meikle, A.W.

doi:10.1002/1097-0045(20000901)44:4<287::aid-pros5>3.0.co;2-z

Cited by 65 publications

(36 citation statements)

References 28 publications

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“…Multiple studies demonstrated that vitamin E inhibits the proliferation of prostate cancer cells in culture (22)(23)(24) as well as in mouse models of the disease (25,26). In virtually all vertebrates, the levels of tocopherol are primarily regulated by the action of TTP, a tocopherolbinding protein that has been well characterized in its primary site of expression, the liver (cf.…”

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

“…In a transgenic model of hepatocellular carcinoma, dietary supplementation with vitamin E brought about a remarkable decrease in DNA damage and in tumor incidence (3). In the prostate, vitamin E was shown to induce cell death and antagonize androgen actions in cultured cells (21)(22)(23)(24) and to delay tumorigenesis in genetic models of the disease in rats (25) and mice (26). Despite the profound anti-carcinogenic effects of vitamin E in the model systems described above, studies on the efficacy of vitamin E in human prostate cancers have been inconclusive.…”

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Tocopherol Transfer Protein Sensitizes Prostate Cancer Cells to Vitamin E

Morley

Thakur

Danielpour

et al. 2010

Journal of Biological Chemistry

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Prostate cancer is a major cause of mortality in men in developed countries. It has been reported that the naturally occurring antioxidant ␣-tocopherol (vitamin E) attenuates prostate cancer cell proliferation in cultured cells and mouse models. We hypothesized that overexpression of the tocopherol transfer protein (TTP), a vitamin E-binding protein that regulates tocopherol status, will sensitize prostate cancer cells to the antiproliferative actions of the vitamin. To test this notion, we manipulated the expression levels of TTP in cultured prostate cells (LNCaP, PC3, DU145, and RWPE-1) using overexpression and knockdown approaches. Treatment of cells with tocopherol caused a time-and dose-dependent inhibition of cell proliferation. Overexpression of TTP dramatically sensitized the cells to the apoptotic effects of ␣-tocopherol, whereas reduction ("knockdown") of TTP expression resulted in resistance to the vitamin. TTP levels also augmented the inhibitory effects of vitamin E on proliferation in semi-solid medium. The sensitizing effects of TTP were paralleled by changes in the intracellular accumulation of a fluorescent analog of vitamin E and by a reduction in intracellular levels of reactive oxygen species and were not observed when a naturally occurring, ligand bindingdefective mutant of TTP was used. We conclude that TTP sensitizes prostate cancer cells to the anti-proliferative effects of vitamin E and that this activity stems from the ability of protein to increase the intracellular accumulation of the antioxidant. These observations support the notion that individual changes in the expression level or activity of TTP may determine the responsiveness of prostate cancer patients to intervention strategies that utilize vitamin E.Prostate cancer is a major public health problem in developed countries, and it constitutes the second leading cause of cancer deaths among males in the United States. Like all malignant diseases, prostate cancer is a culmination of multiple genetic and epigenetic insults, which affect key regulatory features of cell proliferation. Although family history and ethnicity are key risk factors in the susceptibility to prostate cancer, no single gene has been identified as a high penetrance heritable prostate cancer trait to date. Current treatments of prostate cancer rely primarily on surgical and hormonal intervention strategies, coupled with sensitive diagnostic tools aimed at early detection. The incidence, prevalence, and mortality associated with prostate cancer, together with its slow progression from intraepithelial neoplasia (found in men Ͻ30 years of age) to clinical disease (found mostly in men Ͼ50 years of age), make chemoprevention an attractive therapeutic approach for this disease.Accumulation of reactive oxygen species (ROS) 3 and oxidative damage are thought to play important roles during oncogene-induced transformation (1-3) and specifically in the initiation and progression of prostate cancer (4 -6). For example, androgens are shown to increase intracellular ROS lev...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Tocopherol Transfer Protein Sensitizes Prostate Cancer Cells to Vitamin E

Morley

Thakur

Danielpour

et al. 2010

Journal of Biological Chemistry

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“…The epidemiologic study indicated that supplementation of a-vitamin E has a beneficial effect for preventing the incidence and mortality of prostate cancer (7). Besides its antioxidant function, a-vitamin E and its analogues can inhibit transforming growth factor-h (8) and androgen receptor/prostate-specific antigen pathways (9), regulate cell cycle distribution (10,11), arrest DNA synthesis (8), induce apoptosis (12)(13)(14), and reduce invasiveness (15) in prostate cancer cells. a-Tocopherol (a-vitamin E) is the major vitamin E isoform that is preferentially bound by tocopherol transfer protein (TTP) to transport from liver to serum in the human body.…”

Section: Introductionmentioning

confidence: 99%

Tocopherol-Associated Protein Suppresses Prostate Cancer Cell Growth by Inhibition of the Phosphoinositide 3-Kinase Pathway

et al. 2005

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Epidemiologic studies suggested that vitamin E has a protective effect against prostate cancer. We showed here that tocopherol-associated protein (TAP), a vitamin E-binding protein, promoted vitamin E uptake and facilitated vitamin E antiproliferation effect in prostate cancer cells. Interestingly, without vitamin E treatment, overexpression of TAP in prostate cancer cells significantly suppressed cell growth; knockdown of endogenous TAP by TAP small interfering RNA (siRNA) in nonmalignant prostate HPr-1 cells increased cell growth. Further mechanism dissection studies suggested that the tumor suppressor function of TAP was via down-regulation of phosphoinositide 3-kinase (PI3K)/Akt signaling, but not by modulating cell cycle arrest or androgen receptor signaling. Immunoprecipitation results indicated that TAP inhibited the interaction of PI3K subunits, p110 with p85, and subsequently reduced Akt activity. Constitutively active Akt could negate the TAP-suppressive activity on prostate cancer cell growth. Moreover, stable transfection of TAP in LNCaP cells suppressed LNCaP tumor incidence and growth rate in nude mice. Furthermore, TAP mRNA and protein expression levels were significantly down-regulated in human prostate cancer tissue samples compared with benign prostate tissues as measured by reverse transcription-PCR, in situ hybridization, and immunohistochemistry. Together, our data suggest that TAP not only mediates vitamin E absorption to facilitate vitamin E antiproliferation effect in prostate cancer cells, but also functions like a tumor suppressor gene to control cancer cell viability through a non-vitamin E manner. Therefore, TAP may represent a new prognostic marker for prostate cancer progression. (Cancer Res 2005; 65(21): 9807-16)

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“…Vitamin E members could be beneficial against a variety of cancer types, including breast, prostate, and colon through various possible mechanisms, including stimulation of wild-type p53 tumor suppressor gene, down-regulation of mutant p53 proteins, activation of heat shock proteins (HSPs), and possession an anti-angiogenic effect mediated by the blockage of transforming growth factor (TGF) (18)(19)(20)(21)(22)(23). The anticancer activity of vitamin E isoforms have been evinced by several in vitro and in vivo studies.…”

Section: In Vitro and In Vivo Studiesmentioning

confidence: 99%

Vitamin E Transporters in Cancer Therapy

Alqahtani

Kaddoumi

2014

AAPS J

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Abstract. Besides their potent antioxidant activity, vitamin E isoforms demonstrated multiple therapeutic activities among which is their activity against different cancer types, including breast, prostate, and colon cancers. However, the activity of vitamin E isoforms is limited by their low bioavailability following oral administration. In addition to the low solubility, vitamin E isoforms have been established as substrates for several intestinal and hepatic transport proteins. In this review, we present reported anticancer activity of vitamin E family members and the possible utilization of vitamin E and derivatives as chemosensitizers to reverse multidrug resistance when given as part of a delivery system and/or in combination with anticancer therapeutic drugs. Then, the review discusses disposition of vitamin E members and transport proteins that play a role in determining their systemic bioavailability followed by recent advances in vitamin E formulations and delivery strategies.

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Vitamin E and other antioxidants inhibit human prostate cancer cells through apoptosis

Cited by 65 publications

References 28 publications

Tocopherol Transfer Protein Sensitizes Prostate Cancer Cells to Vitamin E

Tocopherol Transfer Protein Sensitizes Prostate Cancer Cells to Vitamin E

Tocopherol-Associated Protein Suppresses Prostate Cancer Cell Growth by Inhibition of the Phosphoinositide 3-Kinase Pathway

Vitamin E Transporters in Cancer Therapy

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