title: Calcium/calmodulin-dependent kinase inhibitor induces  growth inhibition, cell cycle arrest, and apoptosis in human  choriocarcinoma cells.
abstract: KN-93, a membrane-permeant calcium/calmodulin- dependent kinase-selective inhibitor, induces apoptosis in some lines of human tumor cells. We investigated the effect of KN-93 in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of KN-93, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. A WST-1 assay showed that BeWo cells were sensitive to the growth inhibitory effect of KN-93. Cell cycle analysis indicated that exposure to KN-93 decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of externalized phosphatidylserine, by the loss of mitochondrial transmembrane potential, and by antibodies directed against histones from fragmented DNA. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that KN-93 may serve as a therapeutic agent for the treatment of choriocarcinoma.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita 879-5593, Japan. takai@oita-u.ac.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Takai
authors.forename: Tami
authors.initials: T
authors.lastname: Ueda
authors.forename: Naoko
authors.initials: N
authors.lastname: Kira
authors.forename: Terukazu
authors.initials: T
authors.lastname: Ishii
authors.forename: Toshie
authors.initials: T
authors.lastname: Yoshida
authors.forename: Satoko
authors.initials: S
authors.lastname: Koga
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nishida
authors.forename: Kaei
authors.initials: K
authors.lastname: Nasu
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narahara
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001596:Benzylamines / Q000494:pharmacology*; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002822:Choriocarcinoma / Q000378:metabolism / Q000473:pathology; D019925:Cyclin A / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D053148:Caspase 3; D019925:Cyclin A; D019938:Cyclin D1; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides