Abstract

Abstract Breast cancer is the second leading cause of cancer-related deaths among women in Canada and the United States. Metastatic disease is the primary cause of death, despite recent advances in breast cancer treatment strategies and personalized medicine. Novel anti-cancer therapeutics are therefore urgently needed to increase the lifespan of breast cancer patients and prevent metastasis. Piperine (PIP) and piperlongumine (PL), two of the major alkaloids in pepper spices, show inhibitory effects on breast cancer cell growth in vivo and in vitro; however, their lipophilicity has restricted possible clinical application. The encapsulation of these phytochemicals in biodegradable nanoparticles is predicted to increase their water solubility and bioavailability. The goal of this study was first, to optimize a method for the preparation of PIP- and PL-containing polymeric nanoparticles, and second, to explore the inhibitory effects of nanoparticle-encapsulated PIP and PL on breast cancer cell growth and metastatic activity. In contrast to the single oil-in-water emulsion method, PIP- and PL-nanoparticles prepared by the thin-film hydration method were more spherical and showed a uniform size distribution. PIP- and PL- containing nanoparticles decreased the viability of MDA-MB-231 and MDA-MB-468 triple-negative breast cancer cells to the same extend as free PIP and PL. In addition, a noncytotoxic concentration of PIP- and PL-containing nanoparticles inhibited the in vitro migration and invasion of triple-negative breast cancer cells. These findings demonstrate that the encapsulation of PIP and PL within polymeric nanoparticles is possible without compromising the bioactivity of these phytochemicals. PIP- and PL-nanoparticles therefore warrant further investigation in mouse models of breast cancer to establish their utility in the treatment of breast cancer. Citation Format: Javad Ghassemi-Rad, David W. Hoskin. Nanoparticle-encapsulated piperine and piperlongumine inhibit breast cancer cell growth and metastatic activity. [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 3684. doi:10.1158/1538-7445.AM2015-3684

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