Targeting calcium/calmodulin-dependence kinase I and II as a potential anti-proliferation remedy for endometrial carcinomas.
Calcium/calmodulin-dependent kinase (CaMK) I and II expression in endometrial cancer cells correlates with the malignant potential of this tumor, and CaMKI and II are potential therapeutic targets in endometrial cancer. CaMKI and II expression was significantly associated with PCNA-labeling index, clinical stage, histological grade, the presence of invasion to greater than one-half the myometrium, and clinical outcome. All endometrial cancer cell lines examined were sensitive to the growth-inhibitory effect of KN-93, a membrane-permeant CaMKs-selective inhibitor that is competitive with calmodulin. KN-93 induced the G0/G1 arrest and apoptosis, rising hopes that KN-93 may become a useful treatment for endometrial cancers.
Takai
Noriyuki
N
Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, 1-1 Idaigaioka, Hasama-machi, Yufu-shi, Oita, Japan. takai@med.oita-u.ac.jp
Ueda
Tami
T
Nasu
Kaei
K
Yamashita
Satoko
S
Toyofuku
Mayo
M
Narahara
Hisashi
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001596:Benzylamines / Q000494:pharmacology*; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016889:Endometrial Neoplasms; D005260:Female; D006801:Humans; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000970:Antineoplastic Agents; D001596:Benzylamines; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002147:Calmodulin; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides; C517596:CAMK1 protein, human