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A New Process of Cancer Prevention Mediated through Inhibition of Tumor Necrosis Factor Expression¹

Saitama Cancer Center Research Institute, Ina, Kitaadachi-gun, Saitama 362, Japan [M. S., S. O., E. S., N. I., A. K., H. F.]. and Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892 [S-J. K.]

Mechanisms of cancer prevention were studied using structurally different cancer-preventive agents, sarcophytol A, canventol, (-)-epigallocatechin gallate, and tamoxifen, based on our evidence that tumor necrosis factor (TNF-) acts as an endogenous tumor promoter relevant to human carcinogenesis. Pretreatment with the four preventive agents commonly inhibited TNF- mRNA expression and TNF- release in BALB/3T3 cells induced by a tumor promoter, okadaic acid, whereas the expression of early response genes (c-jun, junB, c-fos, and fosB) was enhanced. These results strongly suggest that inhibition of TNF- mRNA expression and its release is a new process of cancer prevention.

¹ This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare for a Second-Term Comprehensive 10-Year Strategy for Cancer Control, a grant from the Ministry of Health and Welfare, a grant from Monbusho International Scientific Research Program, Special Cancer Research from the Ministry of Education, Science and Culture, Japan, and grants from the Foundation of Promotion of Cancer Research, the Princess Takamatsu Cancer Research Fund, the Smoking Research Fund, the Uehara Memorial Life Science Foundation, MOA Health Science Foundation, Suzuken Memorial Foundation, the Asahi Glass Foundation, and the Plant Science Research Foundation of the Faculty of Agriculture Kyoto University.

² Present address: Faculty of Pharmaceutical Sciences, Science University of Tokyo, Tokyo 162, Japan.

³ To whom requests for reprints should be addressed.

Received 3/11/96. Accepted 6/17/96.

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