Nitroxide radical containing nanoparticle as a potential candidate for redox therapeutics in breast cancer

Abstract

Event Abstract Back to Event Nitroxide radical containing nanoparticle as a potential candidate for redox therapeutics in breast cancer Babita Shashni1 and Yukio Nagasaki1, 2, 3 1 Graduate School of Pure and Applied Sciences, University of Tsukuba, Department of Material Science, Japan 2 Graduate School of Comprehensive Human Sciences, University of Tsukuba, Master’s School of Medical Sciences, Japan 3 National Institute for Materials Science (NIMS), Satellite Laboratory, International Center for Materials Nanoarchitectonics (WPI-MANA), Japan Introduction: Elevated basal level of reactive oxygen species (ROS) is a hallmark for cancer cell phenotype. ROS, which is considered to be an oncogenic, has been reported to play a critical role in cancer development, progression and metastasis. Therefore ROS manipulating strategies in cancers may hold a great potential for cancer therapy. Henceforth, in this line we focused our study to investigate the therapeutic efficacy of our pH sensitive and non-sensitive ROS scavenging redox nanoparticle (RNP) [1],[2] (Figure 1) in breast cancer by specific inhibition of ROS regulated proteins associated with cancer metastasis and angiogenesis. Figure 1: Chemical structure representation of a) RNP(N): pH-sensitive and b) RNP(O): non-pH sensitive Materials and Methods: Therapeutic efficacy of RNPs was evaluated by in vitro and in vivo assays. In vitro anti-proliferative, -metastatic and -angiogenic activities were confirmed by cell viability, migration and endothelial migration and tube cell formation assays, respectively, whereas in in vivo the efficacy was investigated in breast cancer mice models by biochemical assays. The mechanisms of anti -metastatic and -angiogenic activities were investigated by expression studies. Results: We confirmed that RNPs significantly restricts proliferation, migration and angiogenesis in breast cancer. Furthermore, we also confirmed RNP directed suppression of ROS regulated migration (NF-kβ and metallo matrix proteases (MMPs)) and angiogenesis (vascular endothelial growth factor (VEGF)) promoting proteins. Anti-metastatic tendency was also confirmed in in vivo breast cancer mice models. Discussion: ROS plays a critical role in cancer cell survival. Considering the dependence of cancer cells on ROS-induced molecular signaling pathways, ROS can thus represent a vulnerable specific target for redox cancer therapeutics. In this study we specifically inhibited the ROS induced metastasis and angiogenesis promoting characteristics of breast cancer cells by down-regulating transcriptional factor NF-kB, MMPs and VEGF (Figure 2). This preclinical evaluation study will thus establish RNP as a potential candidate for breast cancer therapeutics. Figure 2: Schematic representation of mechanism of RNP directed restriction of metastasis and angiogenesis in breast cancer Conclusion: We provide the first molecular evidence of anti-metastatic and anti-angiogenic activities of RNP. This report thus strengthens the role of ROS scavenging nanoparticles as potential candidates for breast cancer therapeutics.