Background: Demethoxycurcumin (DMC) is a curcumin analog with antitumor properties. However, its effects have not been investigated in human head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to verify the antitumor effect and cellular signaling pathways of DMC in FaDu HNSCC cells.
Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell Live/Dead staining, hematoxylin and eosin staining, DAPI staining, FACS, western blotting, caspase-3 activity assay, and nuclear translocation were performed to verify apoptosis and the cellular signaling pathway of DMC in FaDu cells.
Results: DMC increased FaDu cell death, with cells presenting altered morphology and condensed nuclei. DMC increased significantly the apoptotic population of FaDu cells. Sequentially, DMC increased the expression of cleaved caspase-3 and PARP through the up-regulation of pro-apoptotic factors such as FasL, cleaved caspase-8, Bax, Bad, and cleaved caspase-9 and the suppression of anti-apoptotic factors including Bcl-xL and Bcl-2 in FaDu cells. Furthermore, DMC not only suppressed the phosphorylation of NF-κB, but also inhibited the translocation of NF-κB from cytosol to nucleus of FaDu cells.
Conclusions: Present study demonstrates that DMC-induced cell death is mediated caspase-dependently by death receptor-mediated extrinsic and mitochondria-dependent intrinsic apoptosis through the inhibition of NF-κB translocation from the cytosol to the nucleus of FaDu cells. DMC is a curcuminoid with antitumor properties that modulates the NF-κB cellular signaling pathway in FaDu cells. Taken together, this study suggests that DMC has a considerable chemotherapeutic potential for HNSCC.
Keywords: Demethoxycurcumin (DMC); NFκB; apoptosis; caspase; human pharyngeal squamous cell carcinoma.
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