title: Esculetin exerts anti-proliferative effects against non-small-cell lung carcinoma by suppressing specificity protein 1 in vitro.
abstract: Esculetin, a coumarin derivative, is a phenolic compound isolated from Artemisia capillaris, Citrus limonia, and Euphorbia lathyris. Although it has been reported to have anti-inflammatory, anti-oxidant, and anti-proliferative activities in several human cancers, its anti-proliferative activity against non-small-cell lung carcinoma (NSCLC) and the molecular mechanisms involved have not been adequately elucidated. In this study, we used two NSCLC cell lines (NCI-H358 and NCI-H1299) to investigate the anti-proliferative activity and apoptotic effect of esculetin. Our data showed that esculetin-treated cells exhibited reduced proliferation and apoptotic cell morphologies. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly suppressed by esculetin in a dose- and time-dependent manner. Furthermore, the levels of p27 and p21, two key regulators of the cell cycle, were up-regulated by the esculetin-mediated down-regulation of Sp1; the level of a third cell-cycle regulator, survivin, was decreased, resulting in caspase-dependent apoptosis. Therefore, we conclude that esculetin could be a potent anti-proliferative agent in patients with NSCLC.
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, BK21 Plus, Chonbuk National University, Jeonju, Republic of Korea. jichae@jbnu.ac.kr.
authors.forename: Ra H
authors.initials: RH
authors.lastname: Lee
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Jin H
authors.initials: JH
authors.lastname: Cho
authors.forename: Jeong-Yun
authors.initials: JY
authors.lastname: Jang
authors.forename: Il-Keun
authors.initials: IK
authors.lastname: Kong
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: MinSeok S
authors.initials: MS
authors.lastname: Kim
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Chung
authors.forename: Keon B
authors.initials: KB
authors.lastname: Oh
authors.forename: Seon-Min
authors.initials: SM
authors.lastname: Park
authors.forename: Jae-Cheon
authors.initials: JC
authors.lastname: Shin
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Seo
authors.forename: Sungho
authors.initials: S
authors.lastname: Ko
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Chae
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014468:Umbelliferones / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D014468:Umbelliferones; C007628:esculetin