Green tea regulates cell cycle progression in oral leukoplakia

Background. A complete in vitro multi-stage carcinogenesis model for oral cancer was developed to examine chemopreventive strategies. In the present study, the effects of EGCG [(-)-epigallocatechin-3-gallate], the major constituent of green tea, is being examined to understand mechanisms of action. Methods. Effects of EGCG on the cell populations were examined with growth assays, cell cycle analysis, and western blots for retinoblastoma protein (pRB). Results. In each cell type, EGCG inhibited growth, with a decrease in efficacy as cells progressed from normal to cancer. A G₁ block was induced with an increase in the underphosphorylated form of pRB; EGCG- induced inhibition was not permanent, cells recovered, and no resistance developed. Conclusions. Our multistage carcinogenesis model for chemoprevention was effective in defining the chemopreventive value of EGCG. The observation that cancerous oral epithelium was less responsive than normal or dysplastic tissues has implication in the use of this agent, and the mechanisms responsible for this result remain to be defined.