title: Epigallocatechin-3-gallate augments the therapeutic effects of benzo[a]pyrene-mediated lung carcinogenesis.
abstract: 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-2BBaPupon 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. © 2017 BioFactors, 43(4):529-539, 2017.
authors.affiliation: Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX, USA.
authors.forename: Meghan M
authors.initials: MM
authors.lastname: Cromie
authors.affiliation: Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX, USA.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX, USA.
authors.forename: Weimin
authors.initials: W
authors.lastname: Gao
mesh_terms: D001564:Benzo(a)pyrene / Q000633:toxicity*; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005434:Flow Cytometry; D000077156:Gefitinib; D006801:Humans; D011799:Quinazolines / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D011799:Quinazolines; D016159:Tumor Suppressor Protein p53; D001564:Benzo(a)pyrene; D002392:Catechin; C045651:epigallocatechin gallate; D019363:Cytochrome P-450 CYP1A1; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: BaP; EGCG; EGFR; gefitinib; lung carcinogenesis