Resveratrol, a chemopreventive agent, disrupts the cell cycle control of human SW480 colorectal tumor cells.
Resveratrol is a natural polyphenolic compound produced by a number of plants and found in high amount in peanuts, seeds, grapes or berries as source of human nutrition. Epidemiological studies strongly suggest that resveratrol may act as a cancer chemopreventive compound. The mechanism by which resveratrol inhibits cell proliferation was studied in human colorectal tumor SW480 cell line. The results show that resveratrol strongly inhibits cell proliferation at the micromolar range in a time- and dose-dependent manner. Resveratrol appears to block the cell cycle at the transition --> G2/M since inhibition of [(3)H]-thymidine incorporation is not observed, while there is an increase of the cell number in S phase. During this inhibition process, resveratrol increases the content of cyclins A and B1 as well as cyclin-dependent kinases Cdk1 and Cdk2. Moreover, resveratrol promotes Cdk1 phosphorylation. In conclusion, resveratrol exerts a strong inhibition of SW480 human colorectal tumor cell proliferation at least by modulating cyclin and cyclin-dependent kinase activities.
Delmas
Delmas
D
Université de Bourgogne, LBMC, Faculté des Sciences, 6 Bd Gabriel, 21000 Dijon, France.
Passilly-Degrace
Patricia
P
Jannin
Brigitte
B
Cherkaoui Malki
Mustapha
M
Latruffe
Norbert
N
D000230:Adenocarcinoma / Q000473:pathology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D016203:CDC2 Protein Kinase / Q000096:biosynthesis / Q000235:genetics; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D019925:Cyclin A / Q000096:biosynthesis / Q000235:genetics; D019926:Cyclin B / Q000096:biosynthesis / Q000235:genetics; D056744:Cyclin B1; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis / Q000235:genetics; D004261:DNA Replication / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D000077185:Resveratrol; D016196:S Phase / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D016588:Anticarcinogenic Agents; C534699:CCNB1 protein, human; D019925:Cyclin A; D019926:Cyclin B; D056744:Cyclin B1; D006131:Growth Inhibitors; D009363:Neoplasm Proteins; D013267:Stilbenes; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D000077185:Resveratrol