Cancer Chemopreventive Potential of Apples, Apple Juice, and Apple Components

Abstract

Apples (Malus sp., Rosaceae) are a rich source of nutrient as well as non-nutrient components and contain high levels of polyphenols and other phytochemicals. Main structural classes of apple constituents include hydroxycinnamic acids, dihydrochalcones, flavonols (quercetin glycosides), catechins and oligomeric procyanidins, as well as triterpenoids in apple peel and anthocyanins in red apples. Several lines of evidence suggest that apples and apple products possess a wide range of biological activities which may contribute to health beneficial effects against cardiovascular disease, asthma and pulmonary dysfunction, diabetes, obesity, and cancer (reviewed by Boyer and Liu, Nutr J 2004). The present review will summarize the current knowledge on potential cancer preventive effects of apples, apple juice and apple extracts (jointly designated as apple products). In brief, apple extracts and components, especially oligomeric procyanidins, have been shown to influence multiple mechanisms relevant for cancer prevention in in vitro studies. These include antimutagenic activity, modulation of carcinogen metabolism, antioxidant activity, anti-inflammatory mechanisms, modulation of signal transduction pathways, antiproliferative and apoptosis-inducing activity, as well as novel mechanisms on epigenetic events and innate immunity. Apple products have been shown to prevent skin, mammary and colon carcinogenesis in animal models. Epidemiological observations indicate that regular consumption of one or more apples a day may reduce the risk for lung and colon cancer.

Abbreviations

AC:aberrant crypts

ACF:aberrant crypt foci

AE02/-03/-04:apple juice polyphenol extract

AIS:‘alcohol-insoluble substance’

AP-1:activator protein 1

Apaf-1:apoptotic protease activatingfactor 1

APE:apple polyphenol extract

B(a)P:benzo[a]pyrene

bw:body weight

CI:confidence interval

COBRA:combined bisulfite restrictionanalysis

Cox-1:cyclooxygenase-1

Cyp1A:cytochrome P450 1A

DEP-1:density-enhanced protein-tyrosinephosphatase-1

DMBA:7,12-dimethylbenz[a]anthracene

DMH:1,2-dimethylhydrazine

DNMT:DNA methyltransferase

DPPH:1,1-diphenyl-2-picrylhydrazyl

EGCG:(–)-epigallocatechin 3-gallate

EGF:epidermal growth factor

EGFR:epidermal growth factor receptor

FCS:fetal calf serum

Fr.P:procyanidin-enriched fraction P

GJIC:gap-junctional intracellular communication

GSK3β:glycogen synthase kinase 3β

GST:glutathione S-transferase

HDAC:histone deacetylase

IL-2Rα:interleukin-2 receptor α-chain

IQ:2-amino-3-methylimidazo[4,5-f]quinoline

MAP-kinase:mitogen-activated protein kinase

NSP:non-starch polysaccharides

NHS:Nurses Health Study

ODC:ornithine decarboylase

OPC:oligomeric procyanidins

OR:odds ratio

ORAC:oxygen radical absorbance capacity

PARP:poly(ADP-ribose)polymerase

PBMC:peripheral blood mononuclearcells

PGs:prostaglandins

PTM:permeability transition pore

PKC:protein kinase C

ROS:reactive oxygen species

RR:relative risk

SCFA:short-chain fatty acids

TNF-α:tumor necrosis factor-α

TPA:12-O-tetradecanolyphorbol 13-acetate

TRAIL:TNF-related apoptosis-inducing ligand

TSG:tumor suppressor gene

Key words

apples - Malus sp. - Rosaceae - cancer chemoprevention - oligomeric procyanidins - polyphenols

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