title: KO-202125, a sauristolactam derivate, induces apoptosis to prevent KB human oral squamous carcinoma cells through inhibition of cyclooxygenase-2 expression.
abstract: In a previous study, we demonstrated that cyclooxygenase-2 (COX-2) is overexpressed in Korean patients having oral cancer. The goal of this study was to study whether KO-202125 (KO), a sauristolactam derivative in KB human oral squamous carcinoma cells, inhibits the activity of COX-2 enzyme and induces apoptotic cell death. In this study, it was shown that KO inhibited COX-2 mRNA and protein and its catalytic activity (prostaglandin E2), but not COX-1. The antiproliferative effect of KO on KB cells was also examined. The results showed that KO significantly decreased the number of viable cells and showed morphological changes in a concentration-dependent manner. The decrease in cell number was associated with apoptotic cell death evidenced by cleaved poly ADP ribose polymerase (PARP), nuclear fragmentation, sub-G1 population and annexin V positivity. Interestingly, KO is more potent than celecoxib, which is a well-known selective COX-2 inhibitor, although more studies are needed to prove it. Altogether, these results show that KO can act as a potent antioral cancer drug candidate by regulating COX-2 activity.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry and Research of Clinical Medicine, Chonbuk National University, Jeonju, Korea.
authors.forename: Dae-Ho
authors.initials: DH
authors.lastname: Leem
authors.forename: Kyeong-Hee
authors.initials: KH
authors.lastname: Choi
authors.forename: Hye-Suk
authors.initials: HS
authors.lastname: Han
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Shin
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Choi
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
authors.forename: Gu
authors.initials: G
authors.lastname: Kong
authors.forename: Yong-Ki
authors.initials: YK
authors.lastname: Min
authors.forename: Jeong-Seok
authors.initials: JS
authors.lastname: Nam
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Oh
authors.forename: Kyoung-A
authors.initials: KA
authors.lastname: Kim
authors.forename: Ki Han
authors.initials: KH
authors.lastname: Kwon
authors.forename: Nam-Pyo
authors.initials: NP
authors.lastname: Cho
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D054833:Isoindoles / Q000494:pharmacology*; D007624:KB Cells; D007769:Lactams / Q000737:chemistry / Q000494:pharmacology; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D054833:Isoindoles; C547823:KO 202125; D007769:Lactams; D010616:Phenanthrenes; D011720:Pyrazoles; D013449:Sulfonamides; C064673:sauristolactam; D051546:Cyclooxygenase 2; D000068579:Celecoxib