Curcumin inhibits cell cycle progression of immortalized human umbilical vein endothelial (ECV304) cells by up-regulating cyclin-dependent kinase inhibitor, p21WAF1/CIP1, p27KIP1 and p53.
To elucidate possible mechanisms of anti-angiogenic activity by curcumin, we performed cDNA microarray and found that curcumin modulated cell cycle related gene expression. For further confirmation, DNA contents and expression levels of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CDKIs) were examined by FACS analysis and Western blotting, respectively. Curcumin was found to induce G0/G1 and/or G2/M phase cell cycle arrest, up-regulate CDKIs, p21WAF1/CIP1, p27KIP1, and p53, and slightly down-regulate cyclin B1 and cdc2 in ECV304 cells. However, expression level of other cyclins and CDKs were not changed by curcumin. We, therefore, conclude that the up-regulation of CDKIs by curcumin plays a critical role in the regulation of cell cycle distribution in these cells, which may have a major role in anti-angiogenic activity of curcumin.
Laboratory of Cell Biology, Korea Cancer Center Hospital, 139-706 Seoul, Korea.
Myung-Jin
MJ
Park
Eun-Hee
EH
Kim
In-Chul
IC
Park
Hyung-Chan
HC
Lee
Sang-Hyeok
SH
Woo
Jae-Young
JY
Lee
Young-Joon
YJ
Hong
Chang Hun
CH
Rhee
Seung-Hoon
SH
Choi
Bum-Sang
BS
Shim
Seung-Hoon
SH
Lee
Seok-Il
SI
Hong
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014471:Umbilical Veins; D015854:Up-Regulation
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; D003474:Curcumin