Fenofibrate diminishes the self-renewal and metastasis potentials of oral carcinoma stem cells through NF-kappaB signaling.

BACKGROUND/PURPOSE: NF-kappaB family of transcription factors are the major contributors to malignant tumor progression, maintenance of cancer stemness, and enhancement of chemoresistance. Fenofibrate, a lipid-lowering drug, has been considered as a candidate for repurposing in the treatment of cancer through various pathways involved in apoptosis, cell cycle, migration, and invasion, including NF-kappaB. Nevertheless, whether fenofibrate possesses the potential to inhibit cancer stemness remained to be examined. METHODS: Cytotoxicity of fenofibrate was estimated by MTT assay. The cells expressing stemness marker were detected by flow cytometry using ALDEFLUOR Kit. The secondary sphere formation assay was used to assess the self-renewal ability. Transwell system was used to evaluate migration and invasion capacities. NF-kappaB expression was measured by the immunoblotting system. RESULTS: In the present study, we demonstrated that fenofibrate inhibited cell viability, expression of stemness marker, self-renewal, migration, and invasion capacities in a dose-dependent manner. Of note, fenofibrate targeted cancer stem cells of oral squamous cell carcinoma (OSCC-CSCs) and had minimal effects on normal cells. Moreover, administration of fenofibrate at a lower concentration was sufficient to diminish the expression of NF-kappaB p50 and p65. CONCLUSION: This study demonstrated that the inhibitory effects of fenofibrate on OSCC-CSCs properties may be associated with downregulation of NF-kappaB. These results indicated that administration of fenofibrate may serve as an alternative strategy for OSCC therapy.