Mechanistic aspects of green tea as a cancer preventive: Effect of components on human stomach cancer cell lines

It is now well accepted that (-)-epigallocatechin gallate (EGCG) inhibits carcinogenesis in the digestive tract in rodents. To understand the mechanisms of anticarcinogenesis, we first studied growth inhibition by EGCG in human stomach cancer cell lines established at Seoul National University (SNU cell lines). Inhibition by EGCG of [³H]thymidine incorporation into eight SNU cell Lines was examined, in relation to transforming growth factor-β (TGF-β) responsiveness. Various tea polyphenols derived from green tea and black tea induced growth inhibition and apoptosis of human stomach cancer cell line KATO III, and inhibition of tumor necrosis factor-α (TNF-α) release from the cells, in the order of (-)-epicatechin gallate (ECG), EGCG, (-)-epigallocatechin (EGC), teaflavins (TF) and (-)-epicatechin (EC). In addition, we demonstrated that EGCG inhibited TNF-α gene expression in KATO III cells, as well as okadaic acid-induced AP-1 and NF-κB activation. The inhibitory potencies of EGCG for AP-1 and NF-κB binding to DNA were different between KATO III cells and mouse fibroblast cell line BALB/3T3. Thus, EGCG and other tea polyphenols may interact with various transcription factors, in addition to AP-1 and NF-κB, in nuclei of various cells, resulting in inhibition of TNF-α gene expression and TNF-α release.