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

富含 γ-生育酚的生育酚混合物对免疫缺陷小鼠 LNCaP 前列腺肿瘤形成和生长的抑制作用

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

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 g-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 g-TmT increased the levels of a-, 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 g-TmT had strong anticancer activity both in vitro and in vivo. Additional studies are needed to determine the potential preventive effect of g-TmT for prostate cancer in humans.

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