PEG-functionalized zinc oxide nanoparticles induce apoptosis in breast cancer cells through reactive oxygen species-dependent impairment of DNA damage repair enzyme NEIL2

Soumyananda Chakraborti, Samik Chakraborty, Shilpi Saha, Argha Manna, Shruti Banerjee, Arghya Adhikary, Shamila Sarwar, Tapas Hazra, Tanya Das, Pinak Chakrabarti

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)35-47
Number of pages13
JournalFree Radical Biology and Medicine
Volume103
DOIs
StatePublished - Feb 1 2017

Fingerprint

DNA Repair Enzymes
Zinc Oxide
Nanoparticles
Polyethylene glycols
DNA Damage
Reactive Oxygen Species
Repair
Cells
DNA Repair
Apoptosis
Breast Neoplasms
DNA
Enzymes
Sp1 Transcription Factor
Transcription
Switches
Availability
Degradation
Neoplasms

Keywords

  • Apoptosis
  • Breast cancer
  • NEIL2
  • p53
  • PEG-ZnO nanoparticles
  • ROS
  • Sp1

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

PEG-functionalized zinc oxide nanoparticles induce apoptosis in breast cancer cells through reactive oxygen species-dependent impairment of DNA damage repair enzyme NEIL2. / Chakraborti, Soumyananda; Chakraborty, Samik; Saha, Shilpi; Manna, Argha; Banerjee, Shruti; Adhikary, Arghya; Sarwar, Shamila; Hazra, Tapas; Das, Tanya; Chakrabarti, Pinak.

In: Free Radical Biology and Medicine, Vol. 103, 01.02.2017, p. 35-47.

Research output: Contribution to journalArticle

Chakraborti, Soumyananda ; Chakraborty, Samik ; Saha, Shilpi ; Manna, Argha ; Banerjee, Shruti ; Adhikary, Arghya ; Sarwar, Shamila ; Hazra, Tapas ; Das, Tanya ; Chakrabarti, Pinak. / PEG-functionalized zinc oxide nanoparticles induce apoptosis in breast cancer cells through reactive oxygen species-dependent impairment of DNA damage repair enzyme NEIL2. In: Free Radical Biology and Medicine. 2017 ; Vol. 103. pp. 35-47.
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