Curcumin induced modulation of cell cycle and apoptosis in gastric and colon cancer cells.
We have investigated the chemopreventive role of curcumin in gastrointestinal cancers by studying the regulation of proliferation and apoptosis in gastric (KATO-III) and colon (HCT-116) cancer cells. Curcumin inhibited cell proliferation and induced G2/M arrest in HCT-116 cells. Investigation of the levels of cyclins E, D and B by immunoblot analysis showed cyclin B level was unaffected, whereas cyclin D and E levels declined with curcumin in both cell lines. Investigation of cyclin-dependent kinases, Cdk2 and Cdc2, showed activity of Cdc2, but not Cdk2, increased markedly in response to curcumin. In both cell lines, immunoblot analysis indicated that curcumin caused induction of apoptosis as evidenced by cleavage of PARP, caspase-3, and reduction in Bcl-XL levels. Curcumin also stimulated the activity of caspase-8, which initiates Fas signalling pathway of apoptosis. Curcumin therefore appears to exert its anticarcinogenic properties by inhibiting proliferation and inducing apoptosis in certain gastric and colon cancer cells.
Moragoda
L
L
Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan, USA.
Jaszewski
R
R
Majumdar
A P
AP
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D016203:CDC2 Protein Kinase / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000517:prevention & control*; D003474:Curcumin / Q000378:metabolism / Q000494:pharmacology*; D019926:Cyclin B / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000517:prevention & control*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D019926:Cyclin B; D019927:Cyclin E; D006131:Growth Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019938:Cyclin D1; D011065:Poly(ADP-ribose) Polymerases; 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; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003474:Curcumin