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: Ra Ham Lee, Jae-Cheon Shin, Ka-Hwi Kim, Yung Hyun Choi, Jung-Il Chae, Jung-Hyun Shim
• Journal: Oncology reports (Oncol Rep) Vol. 33 Issue 2 Pg. 631-8 (Feb 2015) ISSN: 1791-2431 [Electronic] Greece
• PMID: 25434704 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 6,7-dihydroxyflavone
• Antineoplastic Agents
• Flavones
• Sp1 Transcription Factor
• SP1 protein, human

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• Carcinoma, Squamous Cell (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Flavones (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Mouth Neoplasms (metabolism)
• Sp1 Transcription Factor (metabolism)