Sappanchalcone, a
flavonoid extracted from Caesalpinia sappan, exhibits cytoprotective activity, but the molecular basis for the anticancer effect of
sappanchalcone has not been reported. In this study, we examined whether
sappanchalcone could inhibit the growth of human primary and metastatic
oral cancer cells, and we analyzed the signaling pathway underlying the apoptotic effects of the compound in this process using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium
bromide (MTT) assays, fluorescence microscopy, flow cytometry, and Western blotting.
Sappanchalcone-treated
oral cancer cells showed an increased cytosolic level of
cytochrome c, downregulated Bcl-2 expression, upregulated Bax and p53 expression,
caspase-3 and -9 activation, and
poly (ADP-ribose) polymerase cleavage. Furthermore,
sappanchalcone induced activation of p38,
extracellular signal-regulated kinase (ERK),
c-Jun amino-terminal kinase (JNK), and Nuclear factor k B (NF-κB), as demonstrated by the phosphorylation of each
mitogen-activated protein kinases (MAPKs), the degradation of inhibitor of NF-κα (IκB-α), increased expression of nuclear p65, and NF-κB-
DNA binding. Inhibition of the expression of p38, ERK, JNK, and NF-κB by pharmacological inhibitors reversed
sappanchalcone-induced growth inhibition and apoptosis. These results provide the first evidence that
sappanchalcone suppresses
oral cancer cell growth and induces apoptosis through the activation of p53-dependent mitochondrial, p38, ERK, JNK, and NF-κB signaling. Thus, it has potential as a chemotherapeutic agent for
oral cancer.