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• Zheng, X
• Cui, X
• Khor, T
• Huang, Y
• DiPaola, R
• Goodin, S
• Lee, M
• Yang, C
• Kong, A
• Conney, A
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• Zheng, X
• Cui, X
• Khor, T
• Huang, Y
• DiPaola, R
• Goodin, S
• Lee, M
• Yang, C
• Kong, A
• Conney, A
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• Zheng, X
• Cui, X
• Khor, T
• Huang, Y
• DiPaola, R
• Goodin, S
• Lee, M
• Yang, C
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• Conney, A

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Cancers 2011, 3(4), 3762-3772; doi:10.3390/cancers3043762

Article

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

Xi Zheng ^1,2,* , Xiao-Xing Cui ¹ , Tin Oo Khor ³ , Ying Huang ³ , Robert S DiPaola ² , Susan Goodin ² , Mao-Jung Lee ¹ , Chung S Yang ^1,2 , Ah-Ng Kong ^2,3  and Allan H. Conney ^1,2

¹ Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854, USA ² Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA ³ Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA

* Author to whom correspondence should be addressed.

Received: 25 July 2011; in revised form: 15 September 2011 / Accepted: 15 September 2011 / Published: 28 September 2011

(This article belongs to the Special Issue Prostate Cancer)

Download PDF Full-Text [262 KB, uploaded 28 September 2011 08:55 CEST]

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.

Keywords: prostate cancer; tocopherol; immunodeficient mice; xenograft tumor

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