Procyanidin effects on oesophageal adenocarcinoma cells strongly depend on flavan-3-ol degree of polymerization.
Epidemiological studies have shown that the risk of developing oesophageal adenocarcinoma (OA) is inversely correlated to consumption of fruits and vegetables. Flavan-3-ols are the most abundant subclass of flavonoids in these types of foods. Three apple-derived procyanidin fractions with different average degrees of polymerization (aDP) were characterized and the effects of these fractions and of pure flavan-3-ol monomers ((-)-epicatechin and (+)-catechin) and dimers (B1, B2) on two OA cell lines were investigated. Flavan-3-ol monomers and dimers had no effect on the two cell lines, while apple-derived flavan-3-ol oligomers and polymers induced a time-dependent reduction of cell viability. The reduction in the cell viability was due to the induction of caspase-mediated apoptosis and an arrest of the cell cycle in G0/G1. The magnitude of the reduction in cell viability and induction of apoptosis after exposure to flavan-3-ol oligomeric/polymeric fractions positively correlated with their aDP. These results indicate that only flavan-3-ol oligomers and polymers, but not monomers and dimers, have an effect on the proliferation of OA cells in vitro. As tested flavan-3-ol concentrations are achievable through diet, this study suggests that apple-derived PA may possess chemotherapeutic effects against OA.
Pierini
Roberto
R
Institute of Food Research, Norwich Research Park, Colney, Norwich, UK.
Kroon
Paul A
PA
Guyot
Sylvain
S
Ivory
Kamal
K
Johnson
Ian T
IT
Belshaw
Nigel J
NJ
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D044946:Biflavonoids / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D019281:Dimerization; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D027845:Malus / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D044945:Proanthocyanidins / Q000494:pharmacology*
D044946:Biflavonoids; D005419:Flavonoids; D011108:Polymers; D044945:Proanthocyanidins; C404987:flavan-3-ol; C017674:procyanidin; D002392:Catechin