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

作者：Jeon Young Joo; Bang Woong; Shin Jae Cheon; Park Seon Min; Cho Jung Jae; Choi Yung Hyun; Seo Kang Seok; Choi Nag Jin; Shim Jung Hyun^*; Chae Jung Il

来源：International Journal of Oncology, 2015, 46(6): 2606-2612.

DOI：10.3892/ijo.2015.2972

• beta-lapachone
• oral squamous cell carcinoma
• Sp1
• apoptosis

beta-lapachone (beta-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 beta-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 beta-lap and its underlying signaling pathway. We demonstrated that beta-lap-treated cells significantly reduced cell proliferation but increased DNA condensation and increased sub-G, population in OSCCs. Particularly, beta-lap suppresses activation of transcription factor specificity protein 1 (Sp1) followed by apoptosis in a concentration-dependent manner in OSCCs. Furthermore, beta-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 beta-lap was able to modulate Sp1 transactivation and induce apoptosis through the regulation of cell cycle and apoptosis-related proteins. Therefore, beta-lap may be used in cancer prevention and therapies to improve clinical outcome as an anticancer drug candidate.

• 出版日期2015-6