Effect of EGCG on bronchial epithelial cell premalignant lesions induced by cigarette smoke and on its CYP1A1 expression

Epigallocatechin-3-gallate (EGCG) has been demonstrated to exhibit anticancer effects; however, the mechanisms behind these are not yet clear. The objective of the present study was to assess the effect of EGCG on smoking-induced, precancerous, bronchial epithelial cell lesions and determine a potential protective mechanism. Human bronchial epithelial (HBE) cells were treated with cigarette smoke extract (CSE). Benzopyrene-DNA adducts were detected by immunofluorescence cytochemistry. Changes to microRNA (miRNA) expression levels were detected via microarray. The effects of EGCG on smoke-induced benzopyrene-DNA adduct formation and the subsequent change in miRNA expression were analyzed. Subsequently, the protective effect of EGCG on smoke inhalation-induced precancerous lesions was investigated. The expression levels of miRNA target genes were also analyzed. After CSE treatment, benzopyrene-DNA adducts appeared in HBE cells, along with a resultant change in miRNA expression. EGCG inhibited the effects of CSE exposure; benzopyrene-DNA adduct formation was reduced and miRNA expression changes were suppressed. In vivo, EGCG significantly reduced benzopyrene-DNA adduct formation and the subsequent development of precancerous lesions in rat lungs induced by cigarette smoke inhalation. Moreover, EGCG downregulated CYP1A1 overexpression, a target gene of multiple smoking-induced miRNAs, in rat lungs. EGCG may reduce the risk of lung cancer by downregulating the expression of the key gene CYP1A1, preventing the formation of smoking-induced benzopyrene-DNA adducts and alleviating smoking-induced bronchial epithelial dysplasia and heterogeneity.