Cancer Letters

Cancer Letters

Volume 194, Issue 1, 8 May 2003, Pages 13-19
Cancer Letters

Tart cherry anthocyanins inhibit tumor development in ApcMin mice and reduce proliferation of human colon cancer cells

https://doi.org/10.1016/S0304-3940(02)00583-9Get rights and content

Abstract

Anthocyanins, which are bioactive phytochemicals, are widely distributed in plants and especially enriched in tart cherries. Based on previous observations that tart cherry anthocyanins and their respective aglycone, cyanidin, can inhibit cyclooxygenase enzymes, we conducted experiments to test the potential of anthocyanins to inhibit intestinal tumor development in ApcMin mice and growth of human colon cancer cell lines. Mice consuming the cherry diet, anthocyanins, or cyanidin had significantly fewer and smaller cecal adenomas than mice consuming the control diet or sulindac. Colonic tumor numbers and volume were not significantly influenced by treatment. Anthocyanins and cyanidin also reduced cell growth of human colon cancer cell lines HT 29 and HCT 116. The IC50 of anthocyanins and cyanidin was 780 and 63 μM for HT 29 cells, respectively and 285 and 85 μM for HCT 116 cells, respectively. These results suggest that tart cherry anthocyanins and cyanidin may reduce the risk of colon cancer.

Introduction

Tart cherries contain substantial quantities of anthocyanins in addition to other bioflavonoids [1]. Anthocyanins (Fig. 1), a member of the bioactive phytochemicals, are widely distributed in fruits, vegetables and beans, suggesting that plant-based diets can provide considerable amounts of anthocyanins [2], [3]. Like the vast majority of flavonoids, anthocyanins primarily occur in plants as glycosides. Cyanidin is the major anthocyanin aglycone in tart cherries. Montmorency and Balaton™ tart cherries contain 0.40–0.80 mg/g, respectively, of anthocyanins [1]. These anthocyanins were found to function as antioxidants and cyanidin was shown to inhibit the activities of cyclooxygenase (COX) enzymes in vitro [2], [4]. Several studies have demonstrated that non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the growth of colon tumors in animal models and reduce the risk of colon cancer in humans [5], [6]. In most cases, colon carcinogenesis depends on mutation of the adenomatous polyposis coli (APC) gene, which is considered a gatekeeper in the carcinogenic process [7]. Human APC gene germline mutations cause familial adenomatous polyposis, an autosomal dominantly inherited disease that predisposes affected individuals to develop numerous adenomatous polyps and, ultimately, colorectal cancer. APC gene mutations also are a frequent and early event in sporadic colon cancer. ApcMin mice are a mutant mouse lineage predisposed to multiple intestinal neoplasia (Min) due to a mutation in the murine homolog of the APC gene [8]. The primary phenotype of ApcMin mice is the development of multiple intestinal adenomas.

The objectives of this research were to determine the potential of tart cherry anthocyanins and cyanidin to inhibit intestinal tumor development in ApcMin mice and to determine the potential of anthocyanins and cyanidin to directly inhibit the growth of human colon cancer cells.

Section snippets

Animals and diets

This research was conducted with approval of the Michigan State University All-University Committee on Animal Use and Care. ApcMin mice were produced by mating normal C57BL/6J (Apc+/+) female mice with Min C57BL/6J (ApcMin/+) male mice. ApcMin progeny were identified by a polymerase chain reaction (PCR)-based assay [8] and were randomly assigned to five treatment groups (n=10 per group; equal numbers of males and females) at 4–5 weeks of age and fed treatment diets for 10 weeks. The treatments

Results

Final body weights of mice were significantly influenced by treatment and averaged 22.8, 24.1, 21.3, 19.7, and 25.5 g for mice consuming control diet, anthocyanins, cyanidin, tart cherries, and sulindac, respectively. Final body weights for mice consuming anthocyanins and sulindac were greater (P<0.05) than for mice consuming tart cherries.

Treatments had differential effects on tumor incidence and burden in the various sections of the intestinal tract. Mice consuming anthocyanins, cyanidin, or

Discussion

Our interest in testing the potential of tart cherry anthocyanins and cyanidin to inhibit tumor development in ApcMin mice stemmed from the observation that these compounds inhibit the activities of COX enzymes [4]. Other studies have demonstrated that sulindac (and other NSAIDs) reduce small intestinal tumor multiplicity and size in ApcMin mice [10], [11], [12]. In this study, we found that anthocyanins, cyanidin, and tart cherries (presumably as a source of anthocyanins) all significantly

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Supported by USDA grant 99-35503-8147 (M.G.N., L.D.B.), the Michigan State University Project GREEEN Initiative, and the Cherry Marketing Institute.

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