Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways

Abstract

Objective

Human oral squamous cell carcinoma (OSCC) is a major cause of mortality and morbidity worldwide. There is an urgent need to identify bioactive molecules and potential target genes that could inhibit carcinogenesis for OSCC therapy. Fisetin (3,7,3′,4′-tetrahydroxyflavone), a naturally occurring flavonoid, has been previously shown to have anti-proliferative activities in OSCC; however, its molecular mechanism is unknown.

Methods

Colony formation, cell viability, Boyden chamber, wound healing, and tumor xenograft assays were used to detect the impact of fisetin on OSCC cells in vitro and in vivo. Western blot analysis was used to examine the corresponding protein expression.

Results

Fisetin treatment significantly inhibited proliferation and promoted apoptosis by repressing PAK4 expression. Moreover, fisetin treatment attenuated cell migration by blocking PAK4 signaling pathways. In addition, the tumor xenograft showed anti-tumor growth effects of fisetin exposure in vivo.

Conclusion

Fisetin may represent a potential therapeutic strategy for human OSCC by targeting PAK4 signaling pathways.

Keywords:

• OSCC
• fisetin
• PAK4
• PARP

Funding

This work was supported by the Project of Natural Science Foundation of Liaoning Province (2015020528, 20180530037), and by grants from the National Natural Science Foundation of China (No. 81902701) and College Students’ Innovation and Entrepreneurship Training Projects (201910159001 and 201910159084).

Disclosure

The authors report no conflicts of interest in this work.