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

Abstract

Epigallocatechin‑3‑gallate(EGcG)hasbeendemon‑ strated 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 immuno‑ fluorescence cytochemistry. Changes to microRNA (miRNA) expression levels were detected via microarray. The effects of EGcG on smoke‑induced benzopyrene‑dNA adduct forma‑ tion and the subsequent change in miRNA expression were analyzed. Subsequently, the protective effect of EGcG on smoke inhalation‑induced precancerous lesions was investi‑ gated. 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 expo‑ sure; 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 alle‑ viating smoking‑induced bronchial epithelial dysplasia and heterogeneity.