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

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