Berry anthocyanidins inhibit intestinal polyps and colon tumors by modulation of Src, EGFR and the colon inflammatory environment.

Ashley M Mudd,Jeyaprakash Jeyabalan,Mostafa Fraig,Radha Munagala,Nejat K Egilmez,Tao Gu,Ramesh C Gupta

doi:10.18632/oncoscience.548

Abstract

Colorectal cancer is the third most common form of cancer diagnosed and the third leading class for cancer-related deaths. Given the prevalence of colon cancer worldwide, further insight into developing novel and effective prevention and treatment strategies are warranted. The family of plant pigments known as the anthocyanins has been identified with a variety of health benefits including chemopreventive and therapeutic effects. A limitation to current clinical applications of anthocyanins is the high doses that are required. In order to overcome this limitation, we tested the active moiety, anthocyanidins for chemopreventive and therapeutic effects against colorectal cancer in vivo and in vitro. Treatment with native anthocyanidin mixture (Anthos) from bilberry yielded significant antiproliferative activity against colon cancer cells. Anthos treatment led to significant reductions in polyp and tumor counts in vivo. Reduced Src and EGFR phosphorylation was observed with Anthos treatment, which correlated with downstream targets such as PD-L1 and modulation of the colon inflammatory environment. These results provide a promising outlook on the impact of berry Anthos for the treatment and prevention of familial adenomatous polyposis and colorectal cancer. Results from this study also provide novel mechanistic insight into the chemopreventive and therapeutic activities of Anthos.

Highlights

Colorectal cancer (CRC) is the third leading type of cancer diagnosed and third leading cause of cancer-related deaths within the United States each year
Much progress has been made in the treatment of CRC, it still remains the third leading cause of cancer-related death in the U.S familial adenomatous polyposis (FAP) remains an orphan disease with the only viable treatment option being surgical resection of the colon
The development of alternative prevention and treatment strategies for combating both FAP and CRC are of great importance and represent an unmet need

Summary

Introduction

Colorectal cancer (CRC) is the third leading type of cancer diagnosed and third leading cause of cancer-related deaths within the United States each year. The majority of CRC cases originate from previously benign adenomatous polyps [2]. This process of transformation from benign polyp to malignancy typically takes decades to occur, with approximately 85% of CRC cases occurring after the age of 55 years, according to data acquired by the U.S preventive services www.oncoscience.us task force. A small subset of CRC cases stem from familial syndromes One such precondition for colorectal cancer is familial adenomatous polyposis (FAP). FAP is an autosomal dominant pre-cancerous colorectal condition with an incidence at birth of around 1/8,300 [3] that is caused by mutation(s) in the adenomatous polyposis coli (APC) gene. Even after removal of the colon, individuals with FAP are still at risk for developing adenomas at other sites [6]. Given the limited treatment options for FAP and need for clinicallyeffective chemopreventive measures for CRC, there is a need for additional research for more effective treatment and prevention methods

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Conclusion