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

被引:58
作者
Chakraborti, Soumyananda [1 ,4 ]
Chakraborty, Samik [2 ,5 ]
Saha, Shilpi [2 ]
Manna, Argha [2 ]
Banerjee, Shruti [2 ]
Adhikary, Arghya [2 ,6 ]
Sarwar, Shamila [1 ]
Hazra, Tapas K. [3 ]
Das, Tanya [2 ]
Chakrabarti, Pinak [1 ]
机构
[1] Bose Inst, Dept Biochem, VIIM, P-1-12 CIT Scheme, Kolkata 700054, India
[2] Bose Inst, Div Mol Med, VIIM, P-1-12 CIT Scheme, Kolkata 700054, India
[3] Univ Texas Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA
[4] Jagiellonian Univ, Malopolska Ctr Biotechnol, PL-30387 Krakow, Poland
[5] Harvard Med Sch, Boston Childrens Hosp, Div Nephrol, Boston, MA 02115 USA
[6] Univ Calcutta, CRNN, JD-2, Kolkata 700098, W Bengal, India
关键词
Apoptosis; Breast cancer; NEIL2; P53; PEG-ZnO nanoparticles; ROS; Sp1; ZNO NANOPARTICLES; ANTIBACTERIAL ACTIVITY; LIPID-PEROXIDATION; CARCINOMA-CELLS; DRUG-DELIVERY; DISSOLUTION; RESISTANCE; TOXICITY; PATHWAYS; P53;
D O I
10.1016/j.freeradbiomed.2016.11.048
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:35 / 47
页数:13
相关论文
共 46 条
[1]   ZnO nanorod-induced apoptosis in human alveolar adenocarcinoma cells via p53, survivin and bax/bcl-2 pathways: role of oxidative stress [J].
Ahamed, Maqusood ;
Akhtar, Mohd Javed ;
Raja, Mohan ;
Ahmad, Iqbal ;
Siddiqui, Mohammad Kaleem Javed ;
AlSalhi, Mohamad S. ;
Alrokayan, Salman A. .
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, 2011, 7 (06) :904-913
[2]   Gold nanorods: Their potential for photothermal therapeutics and drug delivery, tempered by the complexity of their biological interactions [J].
Alkilany, Alaaldin M. ;
Thompson, Lucas B. ;
Boulos, Stefano P. ;
Sisco, Patrick N. ;
Murphy, Catherine J. .
ADVANCED DRUG DELIVERY REVIEWS, 2012, 64 (02) :190-199
[3]   Aggregation and Dissolution of 4 nm ZnO Nanoparticles in Aqueous Environments: Influence of pH, Ionic Strength, Size, and Adsorption of Humic Acid [J].
Bian, Shao-Wei ;
Mudunkotuwa, Imali A. ;
Rupasinghe, Thilini ;
Grassian, Vicki H. .
LANGMUIR, 2011, 27 (10) :6059-6068
[4]   Structure and Activity of Lysozyme on Binding to ZnO Nanoparticles [J].
Chakraborti, Soumyananda ;
Chatterjee, Tanaya ;
Joshi, Prachi ;
Poddar, Asim ;
Bhattacharyya, Bhabatarak ;
Singh, Surinder P. ;
Gupta, Vinay ;
Chakrabarti, Pinak .
LANGMUIR, 2010, 26 (05) :3506-3513
[5]   Restoration of p53/miR-34a regulatory axis decreases survival advantage and ensures Bax-dependent apoptosis of non-small cell lung carcinoma cells [J].
Chakraborty, Samik ;
Mazumdar, Minakshi ;
Mukherjee, Shravanti ;
Bhattacharjee, Pushpak ;
Adhikary, Arghya ;
Manna, Argha ;
Chakraborty, Sreeparna ;
Khan, Poulami ;
Sen, Aparna ;
Das, Tanya .
FEBS LETTERS, 2014, 588 (04) :549-559
[6]   New Insights into the Link Between DNA Damage and Apoptosis [J].
De Zio, Daniela ;
Cianfanelli, Valentina ;
Cecconi, Francesco .
ANTIOXIDANTS & REDOX SIGNALING, 2013, 19 (06) :559-571
[7]   Impairment of the DNA repair and growth arrest pathways by p53R2 silencing enhances DNA damage-induced apoptosis in a p53-dependent manner in prostate cancer cells [J].
Devlin, Hong-Lin ;
Mack, Phillip C. ;
Burich, Rebekah A. ;
Gumerlock, Paul H. ;
Kung, Hsing-Jien ;
Mudryj, Maria ;
White, Ralph W. deVere .
MOLECULAR CANCER RESEARCH, 2008, 6 (05) :808-818
[8]   Increased risk of lung cancer associated with a functionally impaired polymorphic variant of the human DNA glycosylase NEIL2 [J].
Dey, Sanjib ;
Maiti, Amit K. ;
Hegde, Muralidhar L. ;
Hegde, Pavana M. ;
Boldogh, Istvan ;
Sarkar, Partha S. ;
Abdel-Rahman, Sherif Z. ;
Sarker, Altaf H. ;
Hang, Bo ;
Xie, Jingwu ;
Tomkinson, Alan E. ;
Zhou, Mian ;
Shen, Binghui ;
Wang, Guanghai ;
Wu, Chen ;
Yu, Dianke ;
Lin, Dongxin ;
Cardenas, Victor ;
Hazra, Tapas K. .
DNA REPAIR, 2012, 11 (06) :570-578
[9]   Studies on antibacterial activity of ZnO nanoparticles by ROS induced lipid peroxidation [J].
Dutta, R. K. ;
Nenavathu, Bhavani P. ;
Gangishetty, Mahesh K. ;
Reddy, A. V. R. .
COLLOIDS AND SURFACES B-BIOINTERFACES, 2012, 94 :143-150
[10]   Cancer nanotechnology: Opportunities and challenges [J].
Ferrari, M .
NATURE REVIEWS CANCER, 2005, 5 (03) :161-171