SCOPE: The aim of this work is to identify which proapoptotic pathway is induced in human colon cancer cell lines, in contact with proanthocyanidins extracted from various berries. METHODS AND RESULTS: Proanthocyanidins (Pcys) extracted from 11 berry species are monitored for proapoptotic activities on two related human colon cancer cell lines: SW480-TRAIL-sensitive and SW620-TRAIL-resistant. Apoptosis induction is monitored by cell surface phosphatidylserine (PS) detection. Lowbush blueberry extract triggers the strongest activity. When tested on the human monocytic cell line THP-1, blueberry Pcys are less effective for PS externalisation and DNA fragmentation is absent, highlighting a specificity of apoptosis induction in gut cells. In Pcys-treated gut cell lines, caspase 8 (apoptosis extrinsic pathway) but not caspase 9 (apoptosis intrinsic pathway) is activated after 3 hours through P38 phosphorylation (90 min), emphasizing the potency of lowbush blueberry Pcys to eradicate gut TRAIL-resistant cancer cells. CONCLUSION: We highlight here that berries Pcys, especially lowbush blueberry Pcys, are of putative interest for nutritional chemoprevention of colorectal cancer in view of their apoptosis induction in a human colorectal cancer cell lines.

Laboratoire d'Innovation Thérapeutique UMR 7200 Faculté de Pharmacie Université de Strasbourg 74 route du Rhin BP 24 67401 Illkirch Cedex France

Laboratoire d'Innovation Thérapeutique UMR 7200 Faculté de Pharmacie Université de Strasbourg 74 route du Rhin BP 24 67401 Illkirch Cedex France ; Department of Medical Chemistry and Biochemistry Palacký University Hněvotínská 3 775 15 Olomouc Czech Republic

Laboratoire d'Innovation Thérapeutique UMR 7200 Faculté de Pharmacie Université de Strasbourg 74 route du Rhin BP 24 67401 Illkirch Cedex France ; UMR 7200 CNRS Faculté de Pharmacie 75 route du Rhin 67400 Illkirch France

Merck Millipore Bioscience Division 78180 Saint Quentin en Yvelines France

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