Capsaicin enhances erlotinib-induced cytotoxicity: Via AKT inactivation and excision repair cross-complementary 1 (ERCC1) down-regulation in human lung cancer cells
Journal
Toxicology Research
Journal Volume
8
Journal Issue
3
Pages
459-470
Date Issued
2019
Author(s)
Abstract
Capsaicin, a natural active ingredient of green and red peppers, has been demonstrated to exhibit anti-cancer properties in several malignant cell lines. Excision repair cross-complementary 1 (ERCC1) has a leading role in the nucleotide excision repair (NER) process because of its involvement in the excision of DNA adducts. Erlotinib (TarcevaR) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated clinical activity in non-small cell lung cancer (NSCLC) cells. However, whether capsaicin and erlotinib could induce synergistic cytotoxicity in NSCLC cells through modulating ERCC1 expression is unknown. In this study, capsaicin decreased the ERCC1 expression in an AKT inactivation dependent manner in two human lung adenocarcinoma cells, namely, A549 and H1975. Enhancement of AKT activity by transfection with constitutive active AKT vectors increased the ERCC1 protein level as well as the cell survival by capsaicin. Moreover, capsaicin synergistically enhanced the cytotoxicity and cell growth inhibition of erlotinib in NSCLC cells, which were associated with the down-regulation of ERCC1 expression and inactivation of AKT in A549 and H1975 cells. Together, these results may provide a rationale to combine capsaicin with erlotinib for lung cancer treatment. ? 2019 The Royal Society of Chemistry.
SDGs
Other Subjects
capsaicin; erlotinib; excision repair cross complementing protein 1; messenger RNA; protein kinase B; A-549 cell line; Akt signaling; Article; cancer inhibition; cancer survival; cell migration; cell survival; cell viability; controlled study; down regulation; drug cytotoxicity; drug potentiation; enzyme inactivation; genetic transfection; human; human cell; lung adenocarcinoma; mRNA expression level; MTS assay; NCI-H1975 cell line; priority journal; protein expression level; real time polymerase chain reaction; Western blotting
Publisher
Royal Society of Chemistry
Type
journal article