title: Coumestrol induces senescence through protein kinase CKII inhibition-mediated reactive oxygen species production in human breast cancer and colon cancer cells.
abstract: An inhibitor of the protein kinase CKII (CKII) was purified from leaves of Glycine max (L.) Merrill and was identified as coumestrol by structural analysis. Coumestrol inhibited the phosphotransferase activity of CKII toward β-casein, with an IC50 of about 5 μM. It acted as a competitive inhibitor with respect to ATP as a substrate, with an apparent Ki value of 7.67 μM. Coumestrol at 50μM resulted in 50% and 30% growth inhibition of human breast cancer MCF-7 and colorectal cancer HCT116 cells, respectively. Coumestrol promoted senescence through the p53-p21(Cip1/WAF1) pathway by inducing reactive oxygen species (ROS) production in MCF-7 and HCT116 cells. The ROS scavenger N-acetyl-l-cysteine (NAC), NADPH oxidase inhibitor apocynin and p22(phox) siRNA almost completely abolished this event. Overexpression of CKIIα antagonised cellular senescence mediated by coumestrol, indicating that this compound induced senescence via a CKII-dependent pathway. Since senescence is an important tumour suppression process in vivo, these results suggest that coumestrol can function by inhibiting oncogenic disease, at least in part, through CKII inhibition-mediated cellular senescence.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Lee
authors.forename: Heung Joo
authors.initials: HJ
authors.lastname: Yuk
authors.forename: Ki-Hun
authors.initials: KH
authors.lastname: Park
authors.forename: Young-Seuk
authors.initials: YS
authors.lastname: Bae
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D003375:Coumestrol / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D007700:Kinetics; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013025:Glycine max / Q000737:chemistry*
chemical_list: D010936:Plant Extracts; D017382:Reactive Oxygen Species; D047390:Casein Kinase II; D003375:Coumestrol