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 the present 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 to 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.

Methyl-Donors Can Induce Apoptosis and Attenuate Both the Akt and the Erk1/2 Mediated Proliferation Pathways in Breast and Lung Cancer Cell Lines

“…Phosphorylation of p53 at Ser15 and Thr55 plays an important role in the nucleocytoplasmic shuttling of p53 [ 49 ]. Inhibition of p-p53 (Thr55) restores the nuclear localization of p53 and sensitizes to DNA damage [ 50 , 51 ], while DNA damage induces phosphorylation at Ser15 [ 52 , 53 ].…”

Carvedilol suppresses malignant proliferation of mammary epithelial cells through inhibition of the ROS‑mediated PI3K/AKT signaling pathway

“…However, in the presence of CAR or AKT inhibitor VIII, the expression of p53 in MCF-10A treated with BaP was unknown. Generally, Ser 15 and Ser 20 in p53 are typically phosphorylated with DNA damage, and Ser 15 is the most common site of phosphorylation (30–32). Therefore, antibodies against p-p53 at Ser 15 and Ser 20 to detect p53 activity by western blotting.…”

Diarylheptanoid 35d overcomes EGFR TKI resistance by inducing hsp70-mediated lysosomal degradation of EGFR in EGFR-mutant lung adenocarcinoma

“…This article contains supporting information ( 23 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ).…”