New TNF-α releasing inhibitors as cancer preventive agents from traditional herbal medicine and combination cancer prevention study with EGCG and sulindac or tamoxifen

Herbal medicines are now attracting attention as potential sources of cancer preventive agents. Using inhibition of tumor necrosis factor-alpha (TNF-alpha) release assay, we studied Acer nikoense, Megusurino-ki in Japanese. Inhibitory potential was found in the leaf extract, and the main active principles were identified as geraniin and corilagin. The IC50 values for TNF-alpha release inhibition were 43 muM for geramin and 76 muM for corilagin, whereas that for (-)-epigallocatechin gallate (EGCG), the green tea polyphenol, as control was 26 KM. Furthermore, treatment with geramin inhibited okadaic acid tumor promotion in a two-stage carcinogenesis experiment on mouse skin. Geraniin and corilagin are present in another well-known Japanese traditional herb, Geranium thunbergii, Genno-shoko in Japanese. Considering seasonal variations of the agents and sites of cultivation of herbs, this paper reviews the significance of geramin as a new cancer preventive agent. In addition, based on accumulated results of green tea as a cancer preventive, we review two important results with EGCG: the synergistic effects of EGCG with sulindac or tamoxifen on cancer preventive activity in PC-9 cells, and cancer prevention of intestinal tumor development in multiple intestinal neoplasia (Min) mice by cotreatment using EGCG with sulindac. We report here new findings on additional gene expression resulting from cotreatment with EGCG and sulindac in PC-9 cells compared with gene expression by EGCG alone or sulindac alone. Overall, our results indicate that, with the continuing spread of cancer chemoprevention as a fundamental medical strategy, both clinicians and researchers should take a closer look at herbal medicine. (C) 2002 Elsevier Science B.V. All rights reserved.