title: Mechanism of sappanchalcone-induced growth inhibition and apoptosis in human oral cancer cells.
abstract: 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.
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Institute of Oral Biology, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Lee
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Byeong-Jun
authors.initials: BJ
authors.lastname: Choi
authors.forename: Deok-Won
authors.initials: DW
authors.lastname: Lee
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Yoon
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D047188:Chalcones / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D000072000:NF-KappaB Inhibitor alpha; C044363:sappanchalcone; D020928:Mitogen-Activated Protein Kinases