Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Dietary factors

H Fujiki MD 1, M Suganuma PhD 2, S Okabe 2, E Sueoka MD 3, N Sueoka MD 3, N Fujimoto MD 2, S Matsuyama MD 2, K Imai PhD 2, K Nakachi PhD 2, T Hashimoto PhD 4, Y Asakawa PhD 4

1 Saitama Cancer Center, 2 Saitama Cancer Center Research Institute, Ina, Kitaadachi-gun, Saitama, 3 Saga Medical School, Nabeshima, Saga, 4 Faculty of Pharmacology, Tokushima Bunri University, Tokushima; Japan,

AIMS: Dietary factors include both carcinogenic and anti-carcinogenic factors. Two of the latter more properly designated as cancer preventives, will be dealt with in this presentation. We also present heterogeneous nuclear ribonucleoprotein B1 (hnRNP B1) as a promising endpoint biomarker of human lung cancer and squamous cell carcinomas. METHODS: Green tea: This is the most effective beverage for cancer prevention in humans. In this presentation, we propose two stages of cancer prevention with green tea: prevention before cancer onset and that following cancer treatment. As for prevention before cancer onset, the endpoint is the delay of cancer onset by drinking green tea, based on results of a prospective cohort study in Saitama Prefecture. We recommend at least 10 Japanese-size cups per day (1.5 - 2.0 g green tea extract) as the effective amount for cancer prevention. One's average daily consumption of green tea can be supplemented with green tea tablets (prepared in collaboration with Tea Experiment Station of Saitama Prefecture) to reach this level. RESULTS: As for cancer prevention following cancer treatment, we found that breast cancer patients of Stage I and II consuming over 5 cups of tea per day showed a lower recurrence rate and a longer disease-free period than those consuming less than 4 cups per day. We include results showing that EGCG with sulindac synergistically enhanced apoptosis of human cancer cell line PC-9, which suggests that a combination of green tea and sulindac will reduce the adverse effects of sulindac in humans. Kava: Looking for another cancer preventive similar to green tea, we paid special attention to the reports of Dr. B. Henderson et al. who found unusually low rates of many cancers in Fiji. It was reported that the people of Fiji commonly drink kava, a beverage prepared from the roots of a tropical plant, Piper methysticum. We have so far isolated five kava lactones from kava extract, and one of these, Kava 3, demethoxyyangonin, significantly inhibited TNF-a release from BALB/3T3 cells treated with okadaic acid, a tumor promoter. It is now well established that induction of TNF-a release from the cells is a practical method to determine the potency of cancer preventive activity. hnRNP B1: hnRNP B1 mRNA is a splicing variant of hnRNP A2 mRNA; hnRNP B1 protein with 37 kDa is an RNA binding protein present in nuclei. We found unique evidence that hnRNP B1 mRNA was significantly elevated in lung cancer tissues, and our hnRNP B1-specific polyclonal antibody recognized hnRNP B1 protein in the nuclei of human cancer cells and squamous cell carcinomas in particular. CONCLUSIONS: Expression of hnRNP B1 protein is a new tumor marker for human lung cancer as well as squamous cell carcinoma of various organs. We are now examining whether cancer preventive dietary factors reduce expression of hnRNP B1 protein, looking toward a new endpoint marker of cancer prevention in humans.

KEY WORDS: green tea, cancer prevention, apoptosis, kava.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on environment & lifestyle.