Innovative strategy of cancer treatment with the combination of green tea catechins and anticancer compounds

Abstract

Human cancer development involves durable genetic changes caused by carcinogens, pro-inflammatory cytokines and chemokines, and simultaneous inflammation in cancer microenvironment. Green tea containing non-toxic anti-inflammatory green tea catechins is an acknowledged cancer preventive. This paper first introduces two results that 10 Japanese-size-cups (150 ml/cup) of green tea per day delayed cancer onset in primary cancer prevention and daily green tea supplemented with tablets of green tea extract equivalent to 10 cups prevented colorectal adenoma recurrence in tertiary cancer prevention. The results allowed us to find synergistic anticancer effects in both in vitro and in vivo experiments with the combinations of (-)-epigallocatechin gallate (EGCG) or green tea extract and two non-steroidal anti-inflammatory drugs (NSAIDs), such as sulindac and celecoxib. We next collected the results of numerous investigators as follows: the combinations of EGCG and 37 anticancer compounds, which include NSAIDs, phytochemicals, and anticancer drugs, generally induced in vitro synergistic anticancer effects on 54 human cancer cell lines derived from various cancer tissues, and the combinations of EGCG, or green tea extract and 13 anticancer compounds showed reduction of tumor volume in xenograft mouse models implanted using various human cancer cell lines. For example, average reduction of tumor volume with combinations, anticancer compounds alone, EGCG alone, or vehicle for control were 70.3%, 33.7%, 26.5%, or 0%, respectively. Especially, the complete elimination of tumor development on human prostate cancer cell line PC-3ML was found in xenograft mouse models treated with combinations of EGCG and paclitaxel, and EGCG and docetaxel. The amount of EGCG necessary for complete elimination of tumor in mice corresponds to 6 - 9 cups of green tea for humans. Moreover, the combination was reported to inhibit stem cell characteristics. The combination resulting in 70.3% reduction of tumor volume makes it possible to innovate cancer treatment, and the cancer patient could achieve improved quality of life without suffering the side effects of anticancer drugs, which results in “the final goal of cancer therapy is the survival of cancer patients with coexistence of cancer cells” presented by Prof. Tomizo Yoshida, a mentor of Japanese pathologists.