Procyanidin effects on oesophageal adenocarcinoma cells strongly depend on flavan‐3‐ol degree of polymerization

Abstract

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.

Low Molecular Weight Procyanidins from Grape Seeds Enhance the Impact of 5-Fluorouracil Chemotherapy on Caco-2 Human Colon Cancer Cells

“…The cytotoxic effects of PC fractions on cancer cells have been reported previously [9], [12], [13]. However, whether these effects occurred through extracellular signalling or following uptake of PCs was not attempted.…”

“…Due to their polymerized structure, cellular absorption is restricted to oligomers with a lower DP, leaving the larger DP molecules for adsorption in the gut lumen following oral administration [10], [11]. A number of studies have reported the polymerization and galloylation of PCs to be responsible for their anti-proliferative effects on transformed cells [9], [12], [13].…”

Oligomeric procyanidins inhibit cell migration and modulate the expression of migration and proliferation associated genes in human umbilical vascular endothelial cells

“…The mean dp was 3.9 l 0.1 (n = 3) as determined by a quantitative thiolysis-HPLC method [16]. The dp 3.9 fraction was further characterized using a semi-quantitative normal phase HPLC with fluorescence detection method which indicated that the oligomer size distribution of the extract was approximately: 15% flavanol dimers, 55% oligomers of dp 3 -7, 24% of polymers of dp 8 -10, and 5% polymers with dp A 10 with monomers present only in trace amounts [17]. A stock solution of the extract was prepared by dissolving the test sample in DMSO (15 mg/mL).…”

Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells

“…The beneficial effects of PAC have been reported against cardiovascular disease, bacterial infection, inflammation and skin complications (12)(13)(14)(15)(16). Moreover, recent studies have demonstrated the therapeutic potential of PAC in vivo and in vitro for the treatment of a wide spectrum of tumor types, including colorectal cancers, lung, brain, prostate, esophagus, oral and breast cancer (17)(18)(19)(20)(21)(22)(23). Due to difficulties in isolation of bioactive constituents studies with cranberry extracts in cancer treatment and on cellular response mechanisms have been limited.…”