title: Downregulation of Sp1 is involved in β-lapachone-induced cell cycle arrest and apoptosis in oral squamous cell carcinoma.
abstract: β-lapachone (β-lap) is a naturally occurring quinone obtained from the bark of lapacho tree (Tabebuia avellanedae) with anti-proliferative properties against various cancers. The present study investigated the cell proliferation and apoptosis effect of β-lap on two oral squamous cell carcinoma lines (OSCCs). We carried out a series of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl-2H-tetrazolium (MTS) assays, 4',6-diamidino-2-phenylindole (DAPI) staining, cell cycle analysis, and western blot analysis to characterize β-lap and its underlying signaling pathway. We demonstrated that β-lap-treated cells significantly reduced cell proliferation but increased DNA condensation and increased sub-G1 population in OSCCs. Particularly, β-lap suppresses activation of transcription factor specificity protein 1 (Sp1) followed by apoptosis in a concentration-dependent manner in OSCCs. Furthermore, β-lap modulated protein expression levels of cell cycle regulatory proteins and apoptosis-related proteins that are known as Sp1 target genes, resulting in apoptosis. Our results collectively indicated that β-lap was able to modulate Sp1 transactivation and induce apoptosis through the regulation of cell cycle and apoptosis-related proteins. Therefore, β-lap may be used in cancer prevention and therapies to improve clinical outcome as an anticancer drug candidate.
authors.affiliation: Department of Oral Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 plus, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jeon
authors.affiliation: Department of Oral Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 plus, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Woong
authors.initials: W
authors.lastname: Bang
authors.affiliation: Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongbuk 790‑834, Republic of Korea.
authors.forename: Jae-Cheon
authors.initials: JC
authors.lastname: Shin
authors.affiliation: Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongbuk 790‑834, Republic of Korea.
authors.forename: Seon-Min
authors.initials: SM
authors.lastname: Park
authors.affiliation: Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors.forename: Jung-Jae
authors.initials: JJ
authors.lastname: Cho
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Animal Science and Technology, Sunchon National University, Suncheon, Republic of Korea.
authors.forename: Kang Seok
authors.initials: KS
authors.lastname: Seo
authors.affiliation: Department of Animal Science, College of Agricultural and Life Science, Chonbuk National University, Jeonju 651-756, Republic of Korea.
authors.forename: Nag-Jin
authors.initials: NJ
authors.lastname: Choi
authors.affiliation: Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
authors.affiliation: Department of Oral Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 plus, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Chae
mesh_terms: D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009285:Naphthoquinones / Q000494:pharmacology*; D016329:Sp1 Transcription Factor / Q000378:metabolism*
chemical_list: D009285:Naphthoquinones; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C014638:beta-lapachone