Synergistic effect of vitamin E and selenium in human prostate cancer cell lines

Venkateswaran, Vasundara; Fleshner, Neil; Klotz, Laurence

doi:10.1038/sj.pcan.4500707

Cited by 45 publications

(30 citation statements)

References 12 publications

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“…We have previously published that vitamin E inhibits the growth of PCa cells in vitro mediated by alteration in cell cycle regulatory molecules, specifically p27 (5). In a second study, we have shown that a combination of E+S was shown to potentiate or act in synergy, thereby enhancing the proportion of cancer prevention (7). It is possible that vitamin E is effective only under certain situations and in selected model systems.…”

Section: Discussionmentioning

confidence: 91%

“…This was particularly evident with a combination of E+S+L that is in line with our previously reported in vitro synergy between micronutrients (7). This is with specific bearing to their antioxidant action and growth-inhibitory effect on PCa cells (7,14,27,28), as well as their additive effects in vitro on androgen receptor target gene expression and oxidative stress reduction in prostate tumors (29).…”

Section: Discussionmentioning

confidence: 99%

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A Combination of Micronutrients Is Beneficial in Reducing the Incidence of Prostate Cancer and Increasing Survival in theLadyTransgenic Model

Venkateswaran

Klotz

Ramani

et al. 2009

Cancer Prevention Research

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We have previously shown that administration of a combination of micronutrients (selenium, vitamin E, and lycopene) inhibits prostate cancer (PCa) development in the Lady transgenic model. In the present study, we examine timing of initiation of micronutrients, and the effect of micronutrient combinations, on PCa development in Lady transgenic model.Transgenic males were randomized to either a control diet; control diet supplemented with human equivalent doses of vitamin E, selenium, and lycopene (E+S+L); or control diet supplemented with vitamin E and selenium (E+S). In separate experiments, the combination of E+S+L was initiated at varying time points (4,8,20, and 36 weeks of age).A combination of E+S+L resulted in a significant reduction in PCa and liver metastasis when intervention was commenced within 8 weeks of age (P < 0.0001). Immunohistochemical analysis revealed a strong correlation between disease-free state with up-regulation of the prognostic marker p27 Kip1 (P < 0.0001) and decreased expression of proliferating cell nuclear antigen and significantly increased apoptotic index (P < 0.0001). On the contrary, a combination of E+S was not effectual in preventing PCa, with a high proportion (84.6%) of animals developing PCa and a small proportion (11.5%) developing high-grade PIN.Early commencement of micronutrients (E+S+L) is beneficial in reducing PCa. Lycopene is an essential component of the combination and effective (when used with E+S) for PCa prevention. These observations provide support for their chemopreventive effect and some clues about their mechanism of action. These key findings will be complementary to the outcome from the Selenium and Vitamin E Chemoprevention Trial.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

A Combination of Micronutrients Is Beneficial in Reducing the Incidence of Prostate Cancer and Increasing Survival in theLadyTransgenic Model

Venkateswaran

Klotz

Ramani

et al. 2009

Cancer Prevention Research

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“…Our laboratory has shown that vitamin E inhibits the growth of prostate cancer cells in vitro mediated by alteration in cell cycle regulatory molecules, specifically p27 (9). A second study carried out in our laboratory revealed that a combination of antioxidants (vitamin E and selenium) is shown to potentate or act in synergy, thereby enhancing the proportion of cancer prevention (42).…”

Section: Discussionmentioning

confidence: 99%

Antioxidants Block Prostate Cancer in Lady Transgenic Mice

Venkateswaran

Fleshner²,

Sugar³

et al. 2004

Cancer Research

108

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The development of chemopreventive agents against prostate cancer would benefit from conclusive evidence of their efficacy in animal models that emulate human disease. To date there has been little in vivo evidence supporting their preventive capabilities. The 12T-10 Lady transgenic model spontaneously develops localized prostatic adenocarcinoma and neuroendocrine cancer followed by metastases, recapitulating the natural history of human prostate cancer in many respects. Using male Lady version of the transgenic adenocarcinoma of the mouse prostate mice, we show that administration of antioxidants (vitamin E, selenium, and lycopene) in the diet dramatically inhibits prostate cancer development and increases the disease free survival. Treatment of animals with the antioxidants resulted in a 4-fold reduction in the incidence of prostate cancer compared with the untreated animals. Prostate cancer developed in 73.68% (14 of 19) and 100% (19 of 19) of the animals from the standard and high fat diet, respectively. In contrast, only 10.53% (2 of 19) and 15.79% (3 of 19; P < 0.0001) of the animals in the standard and high fat diets supplemented with antioxidants developed tumors. The micronutrients were well tolerated with no evidence of antioxidant-related toxicity. Histopathological analysis confirmed absence of cancer in the additive treated groups. Immunohistochemistry demonstrated a strong correlation between disease-free state and increased levels of the prognostic marker p27Kip1 and a marked decrease in proliferating cell nuclear antigen expression. These observations provide support for the chemopreventive effect of these micronutrients and some clues as to their mechanism of action.

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“…The major advantage of chemoprevention compared to other forms of therapy is the lack of systemic toxicity. Another advantage is that according to recent reports chemopreventive agents, when used in combination with conventional therapies, can improve therapeutic response [2]. The relatively long latency in the development of PC makes it an appropriate target for chemoprevention at an early stage.…”

Section: Introductionmentioning

confidence: 98%

Mechanisms of selenium chemoprevention and therapy in prostate cancer

Nadiminty¹,

Gao²

2008

Molecular Nutrition Food Res

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Synergistic effect of vitamin E and selenium in human prostate cancer cell lines

Cited by 45 publications

References 12 publications

A Combination of Micronutrients Is Beneficial in Reducing the Incidence of Prostate Cancer and Increasing Survival in theLadyTransgenic Model

A Combination of Micronutrients Is Beneficial in Reducing the Incidence of Prostate Cancer and Increasing Survival in theLadyTransgenic Model

Antioxidants Block Prostate Cancer in Lady Transgenic Mice

Mechanisms of selenium chemoprevention and therapy in prostate cancer

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