Journal Article

A γ-tocopherol-rich mixture of tocopherols inhibits chemically induced lung tumorigenesis in A/J mice and xenograft tumor growth

Gang Lu, Hang Xiao, Guang-Xun Li, Sonia C. Picinich, Yu-Kuo Chen, Anna Liu, Mao-Jung Lee, Shea Loy and Chung S. Yang

in Carcinogenesis

Volume 31, issue 4, pages 687-694
Published in print April 2010 | ISSN: 0143-3334
Published online January 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp332
A γ-tocopherol-rich mixture of tocopherols inhibits chemically induced lung tumorigenesis in A/J mice and xenograft tumor growth

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The present study investigated the effects of a preparation of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) on chemically induced lung tumorigenesis in female A/J mice and the growth of H1299 human lung cancer cell xenograft tumors. In the A/J mouse model, the lung tumors were induced by either 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; intraperitoneal injections with 100 and 75 mg/kg on Week 1 and 2, respectively) or NNK plus benzo[a]pyrene (B[a]P) (8 weekly gavages of 2 μmole each from Week 1 to 8). The NNK plus B[a]P treatment induced 21 tumors per lung on Week 19; dietary 0.3% γ-TmT treatment during the entire experimental period significantly lowered tumor multiplicity, tumor volume and tumor burden (by 30, 50 and 55%, respectively; P < 0.05). For three groups of mice treated with NNK alone, the γ-TmT diet was given during the initiation stage (Week 0 to 3), post-initiation stage (Week 3 to 19) or the entire experimental period, and the tumor multiplicity was reduced by 17.8, 19.7 or 29.3%, respectively (P < 0.05). γ-TmT treatment during the tumor initiation stage or throughout the entire period of the experiment also significantly reduced tumor burden (by 36 or 43%, respectively). In the xenograft tumor model of human lung cancer H1299 cells in NCr-nu/nu mice, 0.3% dietary γ-TmT treatment significantly reduced tumor volume and tumor weight by 56 and 47%, respectively (P < 0.05). In both the carcinogenesis and tumor growth models, the inhibitory action of γ-TmT was associated with enhanced apoptosis and lowered levels of 8-hydroxydeoxyguanine, γ-H2AX and nitrotyrosine in the tumors of the γ-TmT-treated mice. In cell culture, the growth of H1299 cells was inhibited by tocopherols with their effectiveness following the order of δ-T > γ-TmT > γ-T, whereas α-T was not effective. These results demonstrate the inhibitory effect of γ-TmT against lung tumorigenesis and the growth of xenograft tumors of human lung cancer cells. The inhibitory activity may be due mainly to the actions of δ-T and γ-T.

Journal Article.  5567 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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