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

Abstract

The present study investigated the effects of a preparation of a gamma-tocopherol-rich mixture of tocopherols (gamma-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 mumole each from Week 1 to 8). The NNK plus B[a]P treatment induced 21 tumors per lung on Week 19; dietary 0.3% gamma-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 gamma-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). gamma-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 gamma-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 gamma-TmT was associated with enhanced apoptosis and lowered levels of 8-hydroxydeoxyguanine, gamma-H2AX and nitrotyrosine in the tumors of the gamma-TmT-treated mice. In cell culture, the growth of H1299 cells was inhibited by tocopherols with their effectiveness following the order of delta-T > gamma-TmT > gamma-T, whereas alpha-T was not effective. These results demonstrate the inhibitory effect of gamma-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 delta-T and gamma-T.

• Authors: Gang Lu, Hang Xiao, Guang-Xun Li, Sonia C Picinich, Yu-Kuo Chen, Anna Liu, Mao-Jung Lee, Shea Loy, Chung S Yang
• Journal: Carcinogenesis (Carcinogenesis) Vol. 31 Issue 4 Pg. 687-94 (Apr 2010) ISSN: 1460-2180 [Electronic] England
• PMID: 20097733 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antioxidants
• H2AX protein, human
• Histones
• Nitrosamines
• Leukotriene B4
• Benzo(a)pyrene
• 3-nitrotyrosine
• Tyrosine
• 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
• 8-Hydroxy-2'-Deoxyguanosine
• gamma-Tocopherol
• Deoxyguanosine
• Dinoprostone

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Benzo(a)pyrene
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Deoxyguanosine (analogs & derivatives, analysis)
• Dinoprostone (blood)
• Female
• Histones (analysis)
• Leukotriene B4 (blood)
• Lung Neoplasms (blood supply, chemically induced, prevention & control)
• Mice
• Neovascularization, Pathologic (drug therapy)
• Nitrosamines
• Tyrosine (analogs & derivatives, analysis)
• Xenograft Model Antitumor Assays
• gamma-Tocopherol (pharmacology)