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.