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Int J Oncol. 2015;46(6):2606-12. doi: 10.3892/ijo.2015.2972. Epub 2015 Apr 20.

Downregulation of Sp1 is involved in β-lapachone-induced cell cycle arrest and apoptosis in oral squamous cell carcinoma.

Author information

1
Department of Oral Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 plus, Chonbuk National University, Jeonju 561-756, Republic of Korea.
2
Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongbuk 790‑834, Republic of Korea.
3
Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
4
Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea.
5
Department of Animal Science and Technology, Sunchon National University, Suncheon, Republic of Korea.
6
Department of Animal Science, College of Agricultural and Life Science, Chonbuk National University, Jeonju 651-756, Republic of Korea.

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.

PMID:
25891355
DOI:
10.3892/ijo.2015.2972
[Indexed for MEDLINE]

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