Curcumin-Polyallyhydrocarbon Nanocapsules Potently Suppress 1,2-Dimethylhydrazine-Induced Colorectal Cancer in Mice by Inhibiting Wnt/β-Catenin Pathway

Abstract

Curcumin (CUR), a natural polyphenol found in Curcuma longa (turmeric) rhizomes, has been widely studied for its anticancer activities against various types of tumors, including colorectal cancer (CRC). However, CUR’s therapeutic efficacy is limited by its low bioavailability, short half-life, limited absorption, and rapid and extensive metabolism. Recently, the use of biodegradable and non-toxic polymeric nanocapsules, such as those using polyallyhydrocarbon (PAH), has offered promising delivery systems of poorly absorbed drugs, including CUR. The aim of this study was to determine the in vivo antiproliferative efficacy of intraperitoneally injected CUR-PAH nanocapsules (100 mg/kg body weight; 5 days/week) using a mouse model of 1,2-dimethylhydrazine (DMH)-induced CRC. Histopathological analysis confirmed that the formulated nanocapsulate systems reduced the major neoplastic features of CRC. At the molecular level, CUR-PAH nanocapsules downregulated the Wnt/β-catenin pathway as determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. A statistically significant downregulation in the gene expression levels of Wnt, frizzled (Frz), β-catenin, transcription factor 4 (Tcf4), lymphoid enhancer-binding factor 1 (Lef1), c-Myc, and cyclin D1 (P < 0.01), combined with significant upregulation in the gene expression levels of glycogen synthase kinase (GSK3β) and adenomatous polyposis coli (APC) (P < 0.05), was observed upon post-treatment with CUR-PAH nanocapsules. The observed histopathological and molecular antiproliferative effects were completely absent when using free PAH polymer without CUR, confirming that the anticancer efficacy was solely exerted by the encapsulated CUR. These findings suggest the utility of CUR-PAH nanocapsules as an efficient delivery system with promising therapeutic effects against CRC. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.