Abstract 168A: More effective therapy of cancer by the combination of anticancer drugs with green tea catechins.

Abstract

Abstract Our initial work that (-)-epigallocatechin gallate (EGCG) inhibited tumor promotion on mouse skin, allowed us to develop green tea as cancer preventive in 1987. We and other research groups have further demonstrated that EGCG and green tea extract prevented carcinogenesis in a wide-range of target organs in rodents. In addition, we found that (-)-epicatechin (EC), an inactive catechin synergistically enhances the cancer preventive effects with EGCG, EGC, and ECG, specifically induction of apoptosis, inhibitions of cell growth and TNF-α released from the cells treated with okadaic acid a tumor promoter. The 10-year prospective cohort study of Drs, K. Nakachi and K. Imai in Saitama Prefecture revealed that drinking 10 Japanese-size cups (120 ml/cup) of green tea per day delayed cancer onset in humans by 7.3 years among females and by 3.2 years among males. In 2008, in collaboration with Dr. H. Moriwaki's group, we reported that 10 Japanese-size cups (120 ml/cup) of green tea extract, supplemented with green tea tablets, daily prevented 50% recurrence of colorectal adenomas in patients after polypectomy. In addition, clinical prevention trials of other investigators with green tea demonstrated the prevention of prostate cancer in Italy and high-risk oral premalignant leukoplakia in patients in the US. Cancer patients who consumed green tea and take anticancer drugs would have double prevention. Our in vivo experiments first showed that the combination of sulindac with green tea extract prevented formation of intestinal tumors in Min mice more strongly than sulindac alone or green tea extract alone, and the combination of celecoxib and green tea extract similarly prevented tumor incidence of NNK-induced lung tumors in A/J mice. The enhanced efficacy of the combination of anticancer drugs with EGCG and green tea extract is now well accepted. Recently, numerous research groups reported that the combination of various anticancer drugs with EGCG synergistically inhibited tumor growth in xenograft mouse models implanted using human cancer cell lines of the lung, breast, prostate, liver and stomach. The results of their 11 experiments are briefly summarized. We think the induction of growth arrest and DNA damage-inducible 153 (GADD153, CHOP) gene expression is important for the mechanism of the combination. Since GADD153 protein is a transcription factor and binds to promoter of death receptor (DR) 5, the combination activates both the EGCG-anticancer drug combination apoptosis pathway and the TRAIL-apoptotic pathway. The combination will greatly expand cancer treatments and will result in good prognosis for patients in tertiary cancer prevention. Citation Format: Hirota Fujiki, Tatsuro Watanabe, Atsushi Takahashi, Masami Suganuma. More effective therapy of cancer by the combination of anticancer drugs with green tea catechins. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 168A. doi:10.1158/1538-7445.AM2013-168A