Flavanols and procyanidins of cocoa and chocolate inhibit growth and polyamine biosynthesis of human colonic cancer cells

doi:10.1016/S0304-3835(01)00731-5

Cancer Letters

Volume 175, Issue 2, 25 January 2002, Pages 147-155

https://doi.org/10.1016/S0304-3835(01)00731-5 Get rights and content

Abstract

The effects of cocoa powder and extracts with different amounts of flavanols and related procyanidin oligomers were investigated on the growth of Caco-2 cells. Treatment of the cells with 50 μg/ml of procyanidin-enriched (PE) extracts caused a 70% growth inhibition with a blockade of the cell cycle at the G2/M phase. PE extracts caused a significant decrease of ornithine decarboxylase and S-adenosylmethionine decarboxylase activities, two key enzymes of polyamine biosynthesis. This led to a decrease in the intracellular pool of the polyamines. These observations indicate that polyamine metabolism might be an important target in the anti-proliferative effects of cocoa polyphenols.

Introduction

Foods and beverages deriving from cocoa beans of the tropical fruit Theobroma cacao, have been consumed by humans since at least 460 A.D. [1]. Cocoa products have been used to treat fever, indigestion, liver and lung disorders. Flavanols and their related oligomers have been identified as the major polyphenols in Theobroma cacao [2], but are also found in several other common foods, including apples, almonds, barley, grapes, tea, cinnamon, peanuts, and wine. The flavanols primarly found in cocoa are (−)-epicatechin and (+)-catechin and their related procyanidin oligomers.

Polyphenols of vegetables and fruits have recently attracted increased attention because of their potent anti-oxidant and anti-mutagenic properties [3], [4]. For example, grape seed extracts possess anti-tumour-promoting activity due to their strong anti-oxidant effect [5]. Cocoa procyanidins also exhibit potent anti-oxidant properties [6], [7], [8] and consequently reduce the concentration of reactive oxygen species and low density lipoprotein oxidation in vitro [9], [10]. In addition, cocoa procyanidins show immunomodulatory functions by inhibiting proliferation and by suppression of interleukin-2 production of human T lymphocytes [11], [12]. Cardioprotective effects have also been demonstrated in humans [13], [14], [15].

The anti-proliferative properties of flavanols and procyanidins from cocoa extracts have not been investigated on colon cancer cells. Therefore, we examined the effects cocoa powder and extracts with different amounts of procyanidins on Caco-2 cell growth, a human colonic cancer line, and measured their effects on polyamine biosynthesis, which is known to be enhanced in cancer [16].

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Cocoa powder (CC), crude procyanidin (CP) and procyanidin-enriched (PE) extracts were obtained from Mars Incorporated (Cocoapro™, Hackettstown, USA). Crude procyanidin extract was obtained from cocoa beans by the procedure described by Hammerstone et al. [17]. In brief, approximately 100 g of cocoa beans were frozen in liquid hydrogen and ground to a fine powder in a laboratory mill. The powder was extracted three times with 450 ml hexane to remove lipids. The procedure yielded approximately 45 g

Cocoa samples and Caco-2 cell growth

Dose-dependent effect of CC, CP, and PE extracts were studied on cell proliferation at concentrations ranging from 5 to 50 μg/ml. As shown in Fig. 1, the inhibitory effects of the samples on Caco-2 cell growth was directly related to their flavanol and procyanidin content. CC was the least effective and highest growth inhibition was observed with the PE extracts. At 50 μg/ml, CP extracts with a flavanol and procyanidin content of 501 mg/g, caused only 25% growth inhibition whereas PE extracts

Discussion

The flavanol and procyanidin contents of the cocoa samples is directly related to their anti-proliferative effect on the human colon cancer cell line Caco-2. This is mainly related to the ability of the flavanols and procyanidins to induce non-apoptotic cell death. Cell death was preceeded by the blockade of the cell cycle at the G2/M transition phase. The effects of the cocoa procyanidins are reversible, since cells are resuming growth after 24 h as indicated by the increased amount of cells

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Flavanols and procyanidins of cocoa and chocolate inhibit growth and polyamine biosynthesis of human colonic cancer cells

Abstract

Introduction

Section snippets

Products

Cocoa samples and Caco-2 cell growth

Discussion

Am. J. Clin. Nutr.

Phytochemistry

Am. J. Clin. Nutr.

Lancet

Lancet

Lancet

Life Sci.

Am. J. Clin. Nutr.

Am. J. Clin. Nutr.

J. Immunol. Methods

J. Chromatogr.

Cancer Lett.

Biochim. Biophys. Acta

Biochem. Biophys. Res. Commun.

FEBS Lett.

Polyphenols as cancer chemopreventive agents

J. Cell Biochem.

The relative antioxidant activities of plant-derived polyphenolic flavonoids

Free Rad. Res.