Kinase Assay: |
Toxicol In Vitro. 2011 Dec;25(8):1782-8. | Mechanism of sappanchalcone-induced growth inhibition and apoptosis in human oral cancer cells.[Pubmed: 21963806] | Sappanchalcone, a flavonoid extracted from Caesalpinia sappan, exhibits cytoprotective activity, but the molecular basis for the anticancer effect of Sappanchalcone has not been reported.
METHODS AND RESULTS:
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.
CONCLUSIONS:
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. | Eur J Pharmacol. 2010 Oct 10;644(1-3):230-7. | Effects of sappanchalcone on the cytoprotection and anti-inflammation via heme oxygenase-1 in human pulp and periodontal ligament cells.[Pubmed: 20621084] | Sappanchalcone has been demonstrated to possess several biological effects. However, the molecular mechanism underlying these effects is not fully understood.
METHODS AND RESULTS:
In this study, we examined the effects of Sappanchalcone on hydrogen peroxide (H(2)O(2))-induced cytotoxicity using human dental pulp (HDP) cells, and lipopolysaccharide (LPS)-induced inflammation using human periodontal ligament (HPDL) cells. Sappanchalone concentration proportionately increased heme oxygenase (HO)-1 protein expression and enzyme activity in both HDP and HPDL cells. It also protected HDP cells from H(2)O(2)-induced cytotoxicity and reactive oxygen species production. The cytoprotective effect of Sappanchalcone was nullified by HO-1 inhibitor, Tin protoporphyrin (SnPP). Sappanchalcone is seen to inhibit LPS-stimulated nitric oxide (NO), prostaglandin E(2) (PGE(2)), interlukine-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interlukine-6 (IL-6) and interlukine-12 (IL-12) release in addition to inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in HPDL cells. SnPP, a specific inhibitor of HO-1, partly blocked Sappanchalcone mediated suppression of inflammatory mediator production, in LPS-stimulated HPDL cells. HDP and HPDL cells treated with Sappanchalcone exhibited the transient activation of c-Jun NH2-terminal kinase (JNK) and NF-E2-related factor-2 (Nrf2). The expression of HO-1 protein by Sappanchalcone was significantly reduced by pretreatment with JNK inhibitor.
CONCLUSIONS:
In conclusion, induction of HO-1 is an important cytoprotective mechanism by which Sappanchalcone protects HDP cells from H(2)O(2) and in addition it also exhibits anti-inflammatory effects in LPS-stimulated HPDL cells. Thus, Sappanchalcone could potentially be a therapeutic approach for periodontal, pulpal and periapical inflammatory lesion. |
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