Widdrol induces cell cycle arrest, associated with MCM down-regulation, in human colon adenocarcinoma cells.
Widdrol, an odorous compound extracted from Juniperus chinensis, has been shown to inhibit the in vitro growth of in human cancer cells. This study was conducted on cultured human colon adenocarcinoma HT29 cells to elucidate the possible mechanisms by which widdrol exerts its anti-proliferative activity, which until now has remained poorly understood. It was found that widdrol induces accumulation of sub-G1 phase and arrests in the G1 phase of the cell cycle. Induction of G1 arrest by widdrol was correlated with induction of Chk2, p53 phosphorylation and CDK inhibitor p21 expression as well as inhibition of cyclin E, cyclin-dependent kinase (CDK2) and retinoblastoma protein (pRB). Moreover, mini-chromosome maintenance (MCM) proteins were markedly down-regulated in HT29 cells treated with widdrol. Altogether, these results show widdrol possesses potential anti-cancer activity against colon adenocarcinoma cells by inhibiting their proliferation and inducing cell cycle G1 arrest.
Kwon
Hyun Ju
HJ
Department of Life Science and Biotechnology, Dongeui University, Busan, Republic of Korea.
Hong
Yun Kyung
YK
Park
Cheol
C
Choi
Yung Hyun
YH
Yun
Hee Jung
HJ
Lee
Eun Woo
EW
Kim
Byung Woo
BW
D000230:Adenocarcinoma / Q000378:metabolism*; D001567:Benzocycloheptenes / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000187:drug effects* / Q000378:metabolism; D002469:Cell Separation; D003110:Colonic Neoplasms / Q000378:metabolism*; D015536:Down-Regulation; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D019073:HT29 Cells; D006801:Humans; D047468:Immunoprecipitation; D018653:Juniperus / Q000737:chemistry; D026341:Minichromosome Maintenance 1 Protein / Q000187:drug effects / Q000378:metabolism; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010936:Plant Extracts / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001567:Benzocycloheptenes; D018797:Cell Cycle Proteins; D026341:Minichromosome Maintenance 1 Protein; D009687:Nuclear Proteins; D010936:Plant Extracts; C078670:widdrol; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2