Abstract
Nuclear factor kappa B (NF-κB) inactivation and apoptosis activation have been shown to enhance the anticancer effect of cisplatin in oral squamous cell carcinoma (OSCC). Amentoflavone may suppress NF-κB activity and trigger apoptosis in different types of cancer. The aim of this study was to investigate the anticancer effect and mechanism of amentoflavone in combination with cisplatin in OSCC. We investigated the combination effect and mechanism of amentoflavone and cisplatin via cell viability analysis, flow cytometry-based apoptosis analyses, transwell migration/invasion assay, immunofluorescence staining and western blotting assay. Both amentoflavone and QNZ (NF-κB inhibitor) significantly increased cisplatin-induced cytotoxicity. Amentoflavone reduced cisplatin-triggered NF-κB activity and enhanced cisplatin-induced intrinsic caspase-dependent and independent apoptotic pathways. Moreover, amentoflavone augments cisplatin-suppressed invasion and migration ability of OSCC cells. Inactivation of NF-κB and induction of apoptosis through intrinsic caspase-dependent and independent apoptotic pathways are associated with amentoflavone enhanced anti-OSCC efficacy of cisplatin.
Highlights
The promotion of cisplatin-induced cytotoxicity by amentoflavone was associated with NF-ĸB inhibition in Oral squamous cell carcinoma (OSCC) cells
We identified whether the inhibition of NF-ĸB by QNZ induces the cytotoxicity of cisplatin
After confirming the apoptosis effect of amentoflavone combined with cisplatin, we further aimed to identify which apoptotic pathway was activated by the combination treatment
Summary
Amentoflavone reduced cisplatin-triggered NF-ĸB activity and enhanced cisplatin-induced intrinsic caspasedependent and independent apoptotic pathways. Conclusion: Inactivation of NFĸB and induction of apoptosis through intrinsic caspasedependent and independent apoptotic pathways are associated with amentoflavone enhanced anti-OSCC efficacy of cisplatin. Cisplatin, which inhibits tumor cell growth by inducing DNA damage, is used to treat patients with OSCC [3, 4]. Vitamin D and suberoylanilide hydroxamic acid (SAHA, a histone deacetylase inhibitor), have been found to sensitize OSCC to cisplatin through suppression of nuclear factor kappa B (NF-ĸB) activation [5], as well as to enhance cisplatin-inhibited tumor growth of OSCC by induction of apoptosis [8]. Amentoflavone (AF), a multifunctional compound isolated from herbal plants, has been presented to inhibit tumor cell growth and invasion through reducing NF-ĸB signaling and inducing apoptosis in breast cancer, hepatocellular carcinoma, and glioblastoma [912]. The major purpose of the present study was to investigate the efficacy and mechanism of action of amentoflavone to sensitize OSCC to cisplatin in vitro
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
