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Intake of grape‐derived polyphenols reduces C26 tumor growth by inhibiting angiogenesis and inducing apoptosis
Author(s) -
Walter Allison,
EtienneSelloum Nelly,
Brasse David,
Khallouf Hadeel,
Bronner Christian,
Rio MarieChristine,
Beretz Alain,
SchiniKerth Valérie B.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-149419
Subject(s) - azoxymethane , apoptosis , aberrant crypt foci , angiogenesis , in vivo , colorectal cancer , cyclin d1 , cancer research , chemistry , tunel assay , cancer , neovascularization , grape seed extract , pharmacology , medicine , pathology , biology , cell cycle , biochemistry , colonic disease , microbiology and biotechnology , alternative medicine
This study evaluated the in vivo antitumor activity of grape‐derived polyphenols. BALB/c mice were subcutaneously implanted with C26 colon carcinoma cells, and 2 d later they received either solvent or red wine polyphenols (RWPs) (100 mg/kg/d, human equivalent dose ≈500 mg/d) in the drinking water for 25 d. Wistar rats received either solvent or RWPs (100 mg/kg/d, human equivalent dose ≈1000 mg/d) in the drinking water 1 wk before injection of azoxymethane and were studied 10 wk later. In mice, RWPs inhibited tumor growth by 31%, reduced tumor vascularization and the number of lung metastases, decreased proliferation as indicated by down‐regulation of Ki67, cyclin D1, and UHRF1, and increased apoptosis as indicated by TUNEL staining and active caspase‐3 levels in tumor cells. RWPs reduced expression of VEGF, matrix metalloproteinase (MMP)‐2, MMP‐9, and cyclooxygenase‐2 and increased expression of tumor suppressor genes p16 INK4A , p53, and p73 in tumor cells. In rats, RWPs reduced by 49% the number of azoxymethane‐induced aberrant crypt foci (preneoplastic lesions) in colon. Thus, RWPs effectively reduced the development of colon carcinoma tumors in vivo by blunting tumor vascularization and by inhibiting proliferation and promoting apoptosis of tumor cells subsequent to an up‐regulation of tumor suppressor genes.—Walter, A., Etienne‐Selloum, N., Brasse, D., Khallouf, H., Bronner, C., Rio, M.‐C., Beretz, A., Schini‐Kerth, V. B. Intake of grape‐derived polyphenols reduces C26 tumor growth by inhibiting angiogenesis and inducing apoptosis. FASEB J . 24, 3360–3369 (2010). www.fasebj.org