Epigallocatechin-3-gallate augments the therapeutic effects of benzo[a]pyrene-mediated lung carcinogenesis.

Our previous study found curcumin and vitamin E to have protective effects against benzo[a]pyrene (BaP) exposure in human normal lung epithelial BEAS-2B cells. The first objective of this study was to determine whether epigallocatechin-3-gallate (EGCG) elicited the same response. Co-treatment with 5 µM BaP and 20 µM EGCG in BEAS-2B promoted a significant reduction in cell viability and greater G2/M cell cycle arrest, induction of ROS, and reductions in BaP-induced CYP1A1/CYP1B1/COMT, EGFR, p-Akt (Ser473), p-p53 (Thr55), and survivin mRNA/protein expression, as well as an increase in p-p53 (Ser15). Based on these findings, the second objective was to extend the investigation by developing a novel BaP-transformed BEAS-2B cell line, BEAS-2BBaP , to examine the effects of EGCG when co-administered with gefitinib, an EGFR tyrosine kinase inhibitor. Cell colony formation assay demonstrated in vitro tumorigenic potential of BEAS-2BBaP , which had an overexpression of EGFR. Viability testing revealed gefitinib co-treatment with EGCG resulted in more cell death compared with gefitinib alone. Co-treated cells had greater reductions in gefitinib-induced CYP1A1/CYB1B1, EGFR, cyclin D1, p-Akt (Ser473), and survivin mRNA/protein expression, as well as an increase in p-p53 (Ser15). Therefore, EGCG was found to promote greater cytotoxicity to BEAS-2B co-treated with BaP and BEAS-2BBaP upon gefitinib co-treatment through regulating metabolism enzymes and signaling pathways involving EGFR and p53. These findings suggest that EGCG did not act as a protective compound in BEAS-2B after acute BaP exposure, but has the potential to be a useful adjuvant chemotherapeutic compound when coupled with gefitinib for chemosensitization.