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PEG-functionalized zinc oxide nanoparticles induce apoptosis in breast cancer cells through reactive oxygen species-dependent impairment of DNA damage repair enzyme NEIL2
S CHAKRABORTY, S SAHA, A MANNA, S BANERJEE, A ADHIKARY, S SARWAR, T K HAZRA, T DAS, P CHAKRABARTI
Published in Elsevier Inc.
2017
Volume: 103
   
Pages: 35 - 47
Abstract
We find that PEG functionalized ZnO nanoparticles (NP) have anticancer properties primarily because of ROS generation. Detailed investigation revealed two consequences depending on the level of ROS – either DNA damage repair or apoptosis – in a time-dependent manner. At early hours of treatment, NP promote NEIL2-mediated DNA repair process to counteract low ROS-induced DNA damage. However, at late hours these NP produce high level of ROS that inhibits DNA repair process, thereby directing the cell towards apoptosis. Mechanistically at low ROS conditions, transcription factor Sp1 binds to the NEIL2 promoter and facilitates its transcription for triggering a ‘fight-back mechanism’ thereby resisting cancer cell apoptosis. In contrast, as ROS increase during later hours, Sp1 undergoes oxidative degradation that decreases its availability for binding to the promoter thereby down-regulating NEIL2 and impairing the repair mechanism. Under such conditions, the cells strategically switch to the p53-dependent apoptosis. © 2016 Elsevier Inc.
About the journal
JournalData powered by TypesetFree Radical Biology and Medicine
PublisherData powered by TypesetElsevier Inc.
ISSN0891-5849