SILVER-BASED NANOPARTICLES INDUCE APOPTOSIS IN HUMAN COLON CANCER CELLS MEDIATED THROUGH P53
Satapathy, SR.1, Mohapatra, P.1, Preet, R.1, Das, D.1, Sarkar, B.2, Choudhuri, T.3, Wyatt, MD.4, Kundu, CN.1
1 Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa-751024, India.
2 Nanobiotechnology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa-751024, India.
3 Department of Infection Biology, Institute of Life Science, Nalco square, Bhubaneswar, Orissa- 751021.
4Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA.
My research interest focuses on cancer biology specifically the anti-cancer potentiality of novel metallic and drug formulated nanoparticles. I am interested in eco-friendly synthesis and characterization of metallic and drug formulated nanoparticles. Currently, I am looking for the anti-cancer potentiality of nanoparticles with special focus on colon and breast cancer and also exploring the signaling pathways involved in the nanoparticle mediated programmed cell death. Primarily, I have studied the role of p53 in silver nanoparticle mediated apoptosis in colorectal cancer models and also investigated the interaction between tumor suppressor gene p53 and NFκB.
Aim: The authors have systematically investigated the anticancer potentiality of silver-based nanoparticles (AgNPs) and the mechanism underlying their biological activity in human colon cancer cells. Materials & methods: Starch-capped AgNPs were synthesized, characterized and their biological activity evaluated through multiple biochemical assays. Results: AgNPs decreased the growth and viability of HCT116 colon cancer cells. AgNP exposure increased apoptosis, as demonstrated by an increase in 4´,6-diamidino-2-phenylindole-stained apoptotic nuclei, BAX/BCL-XL ratio, cleaved poly(ADP-ribose) polymerase, p53, p21 and caspases 3, 8 and 9, and by a decrease in the levels of AKT and NF-κB. The cell population in the G1 phase decreased, and the S-phase population increased after AgNP treatment. AgNPs caused DNA damage and reduced the interaction between p53 and NF-κB. Interestingly, no significant alteration was noted in the levels of p21, BAX/ BCL-XL and NF-κB after AgNP treatment in a p53-knockout HCT116 cell line. Conclusion: AgNPs are bona fide anticancer agents that act in a p53-dependent manner.