Nrf-2 transcriptionally activates P21Cip/WAF1 and promotes A549 cell survival against oxidative stress induced by H2 O2

Chemico-biological Interactions
Samarjit JanaShamee Bhattacharjee

Abstract

Cancer cells possess elevated ROS coupled with increased levels of antioxidant enzymes which render them resistant against cytotoxic chemotherapies. Therefore, an understanding of the interaction between key molecules involved in stress adaptive mechanisms is important to innovate strategies against cancer cell chemoresistance. Here, the lung adenocarcinoma cell line A549 with constitutively expressed Nrf2 was found to be more tolerant to H2O2 (0.1, 0.2, 0.5 and 1 mM) than normal lung cell line L132 or p53 null lung cancer cell line H1299. Maximum cytoprotection was observed at 0.2 mM H2O2 accompanied by a significant increase in p21, Nrf2 and antioxidant enzymes in A549 cells. The increased p21 expression was independent of p53 but dependent on Nrf2 as evident from qPCR, Western blotting and dual luciferase assays after silencing Nrf-2 and p53 genes. Highly conserved Nrf-2 binding sites were identified in p21 promoter by bioinformatics and homology modeling which was further confirmed by ChIP and reporter assay.

Citations

Mar 21, 2019·Journal of Molecular Cell Biology·Sofi E ErikssonKlas G Wiman
May 18, 2019·Oxidative Medicine and Cellular Longevity·Emiliano Panieri, Luciano Saso
Jan 27, 2019·International Journal of Molecular Sciences·Marialucia GalloriniRosa Amoroso
Jun 11, 2019·Oxidative Medicine and Cellular Longevity·Xiaolu QuZhendan Shi
Jan 29, 2020·Antioxidants & Redox Signaling·Katarína SmolkováPéter Bai
Jun 26, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Loredana SalernoSebastiano Intagliata
Aug 8, 2021·International Journal of Molecular Sciences·Sonia EmanueleMichela Giuliano

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