Abstract 1856: Sustained release curcumin microparticles delay mammary tumorigenesis in BALB-neuT transgenic mice

Abstract This work examined the chemopreventive efficacy of curcumin delivered by poly(lactide-co-glycolide) (PLGA) microparticles in a HER-2 transgenic mouse mammary tumor model. HER-2 positive breast cancers have a high incidence of metastasis to the brain and are not well treated by conventional means. Curcumin, a dietary polyphenol derived from turmeric, is a powerful antioxidant and has shown chemopreventive activity in vitro. Curcumin suffers from poor oral bioavailability, requiring the need for a controlled release system that could maintain steady plasma levels over a long period of time. Our lab has formulated a curcumin loaded microparticle formulation using the FDA approved polymer, PLGA. Previously published data using this system showed steady curcumin plasma concentrations for a month and efficacy against MDA-MB-231 tumor xenografts (Shahani et al, Cancer Res. 70(11):4443-52). In the present study, Balb-neuT +/- mice were injected subcutaneously with curcumin loaded or empty microparticles at 4, 7 or 12 weeks of age and then once a month thereafter until all mammary pads developed palpable tumors. Mice that started receiving curcumin microparticles at 4 weeks of age showed a difference in age to 50% tumor multiplicity (16 vs 18.5 weeks) and 100% tumor multiplicity (20 vs 22 weeks) compared to those that received control microparticles. No difference was seen in tumor multiplicity when the treatments were started at 7 or 12 weeks of age. Mammary pads from mice that started receiving curcumin treatment at 4 weeks of age showed a significant decrease in Ki-67 expression compared to those from control mice. Curcumin treated mice also showed a decrease in overall percent area of tissue showing abnormal morphology (lobular hyperplasia and carcinoma in situ). These data suggest that curcumin delays tumorigenesis in this model through inhibition of cell proliferation. In summary, sustained release curcumin microparticles show promise as a chemopreventive against Her-2 positive breast cancer. Future studies will examine the effect of starting curcumin treatment at 2 weeks of age (prior to induction of hyperplasia) and determine other potential mechanisms of action of curcumin including inhibition of angiogenesis and induction of apoptosis in this transgenic model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1856. doi:10.1158/1538-7445.AM2011-1856