Induction of GSTP1 and NQO1 mRNA levels by chemopreventive plant-derived mixtures in human lung cancer and normal cells

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One strategy for lung cancer chemoprevention focuses on the use of natural or synthetic agents to modulate the metabolism and disposition of endogenous and environmental carcinogens through upregulation of phase II enzymes. In this study, we applied an in vitro system of assay to investigate the influence of known naturally-occurring mixtures, including green tea (GTE) and broccoli sprout ITC extracts, on the expression of GSTP1 and NQO1 in primary normal human bronchial epithelial (NHBE) cells, immortalized human bronchial epithelial cells (HBEC), and overtly malignant lung adenocarcinoma cells A549. Cells were incubated with 0.5, 1.0, 5.0 µg/ml mixtures (1.0 µg/ml GTE containing 1.2 µM epigallocatechin gallate (EGCG); 1.0 µg/ml broccoli sprout ITC extracts containing 1.4 µM total ITCs) for 24h, 48h and 7 days, respectively. The mRNA expression levels were determined by RNA-specific quantitative RT-PCR previously developed in the laboratory. In NHBE cells, GSTP1 mRNA expression showed 1.7-fold (for 24h) and 2.0-fold (for 7 days) increases after application of 1.0 µg/ml GTE, and a maximum increase of 2.4-fold after 48h application of 5.0 µg/ml GTE. In HBEC cells, GSTP1 mRNA expression showed 2.2- and 2.0-fold increases after 24h application of 1.0 µg/ml GTE and broccoli sprout ITC extracts, respectively. When A549 cells were incubated with the mixtures for 48h, GSTP1 mRNA expression was, however, significantly decreased in a dose-dependent manner by GTE, but not by broccoli sprout ITC extracts. The parallel induction of NQO1 expression was also found in NHBE and HBEC cells, thus providing direct evidence for phase II induction by chemopreventive plant-derived mixtures in human lung. In conclusion, green tea and broccoli sprout ITC extracts are inducers of GSTP1 and NQO1 in the lung and are potentially promising agents for prevention of lung cancer.