Inhibitory Effect of a γ-Tocopherol-Rich Mixture of Tocopherols on the Formation and Growth of LNCaP Prostate Tumors in Immunodeficient Mice

Xi Zheng,Tin Oo Khor,Mao-Jung Lee,Xiao-Xing Cui,Chung S Yang,Allan H Conney,Ying Huang,Susan Goodin,Ah-Ng Kong,Robert S Dipaola

doi:10.3390/cancers3043762

Xi Zheng, Tin Oo Khor + Show 8 more

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https://doi.org/10.3390/cancers3043762

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Abstract

In the present study, we determined the effects of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) on the growth and apoptosis of cultured human prostate cancer LNCaP cells. We also determined the effects of dietary γ-TmT on the formation and growth of LNCaP tumors in immunodeficient mice. In the in vitro study, we found that the activity of γ-TmT was stronger than α-tocopherol for inhibiting the growth and stimulating apoptosis in LNCaP cells. In the animal study, treatment of severe combined immunodeficient (SCID) mice with dietary γ-TmT inhibited the formation and growth of LNCaP xenograft tumors in a dose-dependent manner. Mechanistic studies showed that γ-TmT administration inhibited proliferation as reflected by decreased mitosis and stimulated apoptosis as reflected by increased caspase-3 (active form) expression in LNCaP tumors. In addition, dietary administration of γ-TmT increased the levels of α-, γ- and δ- tocopherol in plasma, and increased levels of γ- and δ- tocopherol were also observed in the prostate and in tumors. The present study demonstrated that γ-TmT had strong anticancer activity both in vitro and in vivo. Additional studies are needed to determine the potential preventive effect of γ-TmT for prostate cancer in humans.

Highlights

Vitamin E exists in eight different forms that include four tocopherols and four tocotrienols.Tocopherols are plant-derived polyphenolic compounds
A previous clinical trial using α-tocopherol and β-carotene showed that fewer cases of prostate cancer were diagnosed among those who received α-tocopherol than among those who did not [8], the results of a large-scale human trial using α-tocopherol and selenium failed to show a preventive effect on prostate cancer [9]
In the in vitro study, we found that γ-tocopherol-rich mixture of tocopherols (γ-TmT) had stronger effects for inhibiting the growth and stimulating apoptosis than α-tocopherol in LNCaP cells

Summary

Introduction

Vitamin E exists in eight different forms that include four tocopherols and four tocotrienols.Tocopherols are plant-derived polyphenolic compounds. Vitamin E exists in eight different forms that include four tocopherols and four tocotrienols. Depending upon the number and position of methyl groups on the chromanol ring, they exist as α-, β-, γ- or δ-tocopherol [1,2]. Α-tocopherol is the predominant form of vitamin E in plasma and tissues and is the form that has drawn the most attention. Several epidemiological studies have shown that a lower vitamin E nutritional status is associated with increased risk of certain types of cancers [3,4,5,6,7], but the results from epidemiological studies on the protective role of tocopherols against prostate cancer are inconsistent [3]. A possible explanation for the negative outcome of this study was that α-tocopherol may not have been the right form of tocopherol for the prevention of prostate cancer

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