Abstract

Colon cancer is one of the leading causes of cancer-associated death worldwide. The prognosis for advanced colorectal cancers remains dismal, mainly due to the propensity for metastatic progression. Accordingly, there is a need for effective anti-metastasis therapeutic agents. Since a great body of research has indicated anticancer effects for curcumin, we investigated the effects of dendrosomal curcumin (DNC) on cellular migration and adhesion of human SW480 cells and possible molecular mechanisms involved. Different methods were applied in this study including MTT, Scratch and adhesion assays as well as real-time PCR and transwell chamber assays. Based on the results obtained, DNC inhibits metastasis by decreasing Hef 1, Zeb 1 and Claudin 1 mRNA levels and can reduce SW480 cell proliferation with IC50values of 15.9, 11.6 and 7.64 μM at 24, 48 and 72 h post-treatment. Thus it might be considered as a safe formulation for therapeutic purpose in colorectal cancer cases.

Highlights

  • Colorectal cancer (CRCs) is the third most common cancer in men and the second in women (Ferlay et al, 2008; Ku et al, 2012)

  • Most of the drugs available for treatment of colorectal cancer are not appropriate for their high cost, toxicity and not guaranteeing against metastasis and cancer recurrence (Kimelman and Xu, 2006; Huei, 2008; Das et al, 2010; Babaei et al, 2012). In view of these facts, the need for a more efficient treatment for cases affected with metastatic colorectal cancers which make up the majority of patients cannot be disregarded

  • Given the well-known limitations of malignant colorectal cancer treatment strategies, the role of dendrosomal curcumin (DNC) on the cell metastasis and mechanisms involved in this process in SW480 cells-a highly tumorigenic and invasive colon carcinoma cell line (Trainer et al, 1988) with increased expression of genes Zeb 1, Claudin 1, Hef 1 and matrix-metalloproteinases (MMP)-1,2,3,7 and -9 (Nobutomo et al, 2001; Meiko et al, 2002; Hlubek et al, 2004; Murray, 2004; Karadag et al, 2005; Tian et al, 2009; Qin et al, 2010; Amar et al, 2011; Li et al, 2011; Seo and Kim, 2011; Sanchez-Tillo et al, 2013; Wang et al, 2013; Zhao et al, 2013) and hyperactive WNT and Hedgehog signaling pathways (Korinek, 1997; Qualtrough et al, 2004), was evaluated

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Summary

Introduction

Colorectal cancer (CRCs) is the third most common cancer in men and the second in women (Ferlay et al, 2008; Ku et al, 2012). There are few studies reporting the effect of curcumin on cancer cell metastasis, adhesion to extracellular matrix (Bharat et al, 2005; Aggarwal et al, 2006; Hong et al, 2006) and there is no available information to address the effects of curcumin on migration and invasion of SW480 cells, a cellular model of metastatic colorectal cancer (Trainer et al, 1988). The purpose of this study is to evaluate the effects of dendrosomal curcumin on cell migration and adhesion to extracellular matrix of SW480 cells and possible molecular mechanisms involved. The results obtained showed that dendrosomal curcumin concentration dependently inhibits the migration and adhesion to ECM in SW480 cells This inhibitory activity was mediated by downregulation of Zeb 1, Claudin 1 and Hef 1 genes in SW480 cells. Our findings suggest that dendrosomal curcumin might have an anti-metastatic effect by decreasing invasiveness of cancer cells and could be assumed as a powerful candidate for developing preventive agents for tumor metastasis

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