Apoptotic effects of 7,8-dihydroxyflavone in human oral squamous cancer cells through suppression of Sp1

Lee,Ra Ham; Shin,Jae-Cheon; Kim,Ka-Hwi; Choi,Yung Hyun; Chae,Jung-Il; Shim,Jung-Hyun

doi:10.3892/or.2014.3632

Apoptotic effects of 7,8-dihydroxyflavone in human oral squamous cancer cells through suppression of Sp1

Authors:
- Ra Ham Lee
- Jae-Cheon Shin
- Ka-Hwi Kim
- Yung Hyun Choi
- Jung-Il Chae
- Jung-Hyun Shim
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Affiliations: Department of Oral Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 plus, Chonbuk National University, Jeonju 651-756, Republic of Korea, Pohang Center for Evaluation of Biomaterials, Pohang Technopark, Jigok-dong, Pohang, Gyeongbuk 790-834, Republic of Korea, Natural Medicine Research Institute, Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam 534-729, Republic of Korea, Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea
Published online on: November 27, 2014 https://doi.org/10.3892/or.2014.3632
Pages: 631-638

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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.

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