Abstract 2811: Silver nanoparticles protect human keratinocytes from deleterious effects of ultraviolet radiation: Implications for skin cancer chemoprevention

Abstract

Abstract Skin cancer is the most common form of cancer worldwide and its incidence has been increasing at an alarming rate in the United States. A solar ultraviolet (UV) radiation, particularly UVB, is the main etiological cause of skin carcinogenesis due to its DNA damaging ability. Therefore, multidisciplinary scientific research has placed specific emphasis on finding novel ways for skin cancer chemoprevention. Here, we provide first experimental evidence for chemopreventive efficacy of silver-nanoparticles (AgNPs) against UVB-induced DNA damage and apoptosis in immortalized human epidermal keratinocytes (HaCaT). AgNPs synthesized by chemical reduction method were characterized for their physicochemical properties. The nanoparticles were spherical (> 90%) in shape, in the size range of 20-50 nm, and had net negative surface charge with an average zeta potential of - 47.7 mV. AgNPs were largely non-toxic to HaCaT cells and their pretreatment protected them from UVB-induced apoptosis. Significant reduction in cyclobutane pyrimidine dimer (CPD) formation upon UVB exposure was also observed in AgNPs-pretreated HaCaT cells. In addition, AgNPs pre-treatment leads to G1 phase arrest of cell cycle in UVB-exposed HaCaT cells thus allowing sufficient time for CPDs repair. Moreover, enhanced AgNPs internalization and localization into cytoplasmic and nuclear compartments was observed by UVB irradiated HaCaT cells. Furthermore, AgNPs pretreatment altered the expression of various genes involved in cell-cycle, apoptosis and nucleotide-excision repair in UVB-irradiated HaCaT cells. Together, these findings clearly suggest the potential utility of AgNPs as novel chemopreventive agents against UVB-induced skin carcinogenesis. Citation Format: Sumit Arora, Nikhil Tyagi, Arun Bhardwaj, Lilia Rusu, Rohan Palanki, Ajay P. Singh, James E. Carter, Seema Singh. Silver nanoparticles protect human keratinocytes from deleterious effects of ultraviolet radiation: Implications for skin cancer chemoprevention. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2811. doi:10.1158/1538-7445.AM2015-2811