title: Apoptotic effects of 7,8-dihydroxyflavone in human oral squamous cancer cells through suppression of Sp1.
abstract: 7,8-Dihydroxyflavone (7,8-DHF) is a member of the flavonoid family and has recently been identified as a brain-derived neurotrophic factor mimetic that selectively activates tropomyosin-receptor kinase B with high affinity. The antioxidant and anticancer effects of 7,8-DHF have been reported. However, the pharmacological mechanisms of 7,8-DHF in oral cancer are unclear. Thus, we investigated the mechanisms of the antiproliferative action of 7,8-DHF on HN22 and HSC4 oral squamous cell carcinoma cell lines. We demonstrated that 7,8-DHF decreased cell growth and induced apoptosis in the HN22 and HSC4 cells through regulation of specificity protein 1 (Sp1) using the MTS assay, DAPI staining, Annexin V, propidium iodide staining, reverse transcription-polymerase chain reaction, immunocytochemistry, pull-down assay and western blot analysis. The results showed that the Sp1 protein bound with 7,8-DHF in the HN22 and HSC4 cells. Taken together, the results suggest that 7,8-DHF could modulate Sp1 transactivation and induce apoptotic cell death by regulating the cell cycle and suppressing antiapoptotic proteins. Furthermore, 7,8-DHF may be valuable for cancer prevention and better clinical outcomes.
authors.affiliation: Department of Oral Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 plus, Chonbuk National University, Jeonju 651-756, Republic of Korea.
authors.forename: Ra Ham
authors.initials: RH
authors.lastname: Lee
authors.affiliation: Pohang Center for Evaluation of Biomaterials, Pohang Technopark, Jigok-dong, Pohang, Gyeongbuk 790-834, Republic of Korea.
authors.forename: Jae-Cheon
authors.initials: JC
authors.lastname: Shin
authors.affiliation: Natural Medicine Research Institute, Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam 534-729, Republic of Korea.
authors.forename: Ka-Hwi
authors.initials: KH
authors.lastname: Kim
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 Oral Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 plus, Chonbuk National University, Jeonju 651-756, Republic of Korea.
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Chae
authors.affiliation: Natural Medicine Research Institute, Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam 534-729, Republic of Korea.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism*
chemical_list: C485383:6,7-dihydroxyflavone; D000970:Antineoplastic Agents; D047309:Flavones; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human