title: PEG-functionalized zinc oxide nanoparticles induce apoptosis in breast cancer cells through reactive oxygen species-dependent impairment of DNA damage repair enzyme NEIL2.
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.
authors.affiliation: Department of Biochemistry, Bose Institute, P-1/12 C.I.T. Scheme, VIIM, Kolkata 700054, India.
authors.forename: Soumyananda
authors.initials: S
authors.lastname: Chakraborti
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12 C.I.T. Scheme, VIIM, Kolkata 700054, India.
authors.forename: Samik
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12 C.I.T. Scheme, VIIM, Kolkata 700054, India.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Saha
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12 C.I.T. Scheme, VIIM, Kolkata 700054, India.
authors.forename: Argha
authors.initials: A
authors.lastname: Manna
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12 C.I.T. Scheme, VIIM, Kolkata 700054, India.
authors.forename: Shruti
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12 C.I.T. Scheme, VIIM, Kolkata 700054, India.
authors.forename: Arghya
authors.initials: A
authors.lastname: Adhikary
authors.affiliation: Department of Biochemistry, Bose Institute, P-1/12 C.I.T. Scheme, VIIM, Kolkata 700054, India.
authors.forename: Shamila
authors.initials: S
authors.lastname: Sarwar
authors.affiliation: Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, TX 77555-1079, United States.
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Hazra
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12 C.I.T. Scheme, VIIM, Kolkata 700054, India. Electronic address: tanya@jcbose.ac.in.
authors.forename: Tanya
authors.initials: T
authors.lastname: Das
authors.affiliation: Department of Biochemistry, Bose Institute, P-1/12 C.I.T. Scheme, VIIM, Kolkata 700054, India. Electronic address: pinak@jcbose.ac.in.
authors.forename: Pinak
authors.initials: P
authors.lastname: Chakrabarti
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms; D045647:DNA Glycosylases / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D053768:Metal Nanoparticles / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015034:Zinc Oxide / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D011092:Polyethylene Glycols; D045647:DNA Glycosylases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; C473642:NEIL2 protein, human; D015034:Zinc Oxide
keywords: Apoptosis; Breast cancer; NEIL2; PEG-ZnO nanoparticles; ROS; Sp1; p53