Epigallocatechin‐3‐gallate augments the therapeutic effects of benzo[a]pyrene‐mediated lung carcinogenesis
Year: 2017
Type: article
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‐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. © 2017 BioFactors, 43(4):529–539, 2017
Source: BioFactors
DOI: 10.1002/biof.1355
Authors: Meghan M. Cromie, Zhongwei Liu, Weimin Gao
Institution: Texas Tech University
Language: English
Topic: Tea Polyphenols and Effects
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2594908491