Quercetin and EGCG Exhibit Chemopreventive Effects in Cholangiocarcinoma Cells via Suppression of JAK/STAT Signaling Pathway

Abstract

Quercetin and epigallocatechin-3-gallate (EGCG) are dietary phytochemicals with antiinflammatory and antitumor effects. In the present study, we examined the effects of these two compounds on Janus-like kinase (JAK)/signal transduction and transcription (STAT) pathway of cholangiocarcinoma (CCA) cells, because CCA is one of the aggressive cancers with very poor prognosis and JAK/STAT pathway is critically important in inflammation and carcinogenesis. The results showed that the JAK/STAT pathway activation by proinflammatory cytokine interleukin-6 and interferon-γ in CCA cells was suppressed by pretreatment with quercetin and EGCG, evidently by a decrease of the elevated phosphorylated-STAT1 and STAT3 proteins in a dose-dependent manner. The cytokine-mediated up-regulation of inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 (ICAM-1) via JAK/STAT cascade was abolished by both quercetin and EGCG pretreatment. Moreover, these flavonoids also could inhibit growth and cytokine-induced migration of CCA cells. Pretreatment with specific JAK inhibitors, AG490 and piceatannol, abolished cytokine-induced iNOS and ICAM-1 expression. These results demonstrate beneficial effects of quercetin and EGCG in the suppression of JAK/STAT cascade of CCA cells. Quercetin and EGCG would be potentially useful as cancer chemopreventive agents against CCA.

Antitumor effects of candidone extracted from <i>Derris indica</i> (Lamk) Bennet in cholangiocarcinoma cells

“…They mediate anticancer effects with selective toxicity towards cancer cells [16]. The antitumor effect of flavonoids including luteolin, quercetin, and EGCG in CCA are mediated through the suppression of JAK/STAT signaling [9,17] and induction of mitochondrial cell death pathway [18]. In the present study, candidone showed a cytotoxic effect against two CCA cells, KKU-M156 and KKU-M213, in the micromolar range.…”

Luteolin Arrests Cell Cycling, Induces Apoptosis and Inhibits the JAK/STAT3 Pathway in Human Cholangiocarcinoma Cells

“…In fact, a compound with the ability to block the metastasis-associated steps could be a potential candidate for cancer chemoprevention and chemotherapy. It has been reported that the activation of STAT3 modulates the transcription of a variety of genes involved in the regulation of metastasis process, including ICAM-1 (Senggunprai et al, 2013) and vascular endothelium growth factor (Zhao et al, 2012). In this study, it was found that IL-6 increased the motility of CCA cells, and the specific JAK inhibitor, AG490, significantly decreased IL-6-dependent cell migration.…”

“…Cell migration was assessed using a wound healing assay as a method described previously (Senggunprai et al, 2013). Briefly, KKU-M156 cells (1.5 x 10 5 ) were seeded into a 24-well plate and incubated overnight in Ham's F12 medium, supplemented with 10% fetal calf serum.…”

“…We have recently reported that STAT3 activation in CCA cells leads to the up-regulation of expression of intercellular adhesion molecule-1 (ICAM-1), which is an adhesion molecule involved in cell migration and invasion (Senggunprai et al, 2013). In this study, it was then explored as to whether the JAK/STAT3 pathway activation mediates the migration of CCA cells.…”

In silico database screening of potential targets and pathways of compounds contained in plants used for psoriasis vulgaris

“…In diabetes-induced glomerular hypertrophy in mice, low-dose ursolic acid ameliorated deterioration via suppression of diabetes-induced activations of STAT3, MAPK3/1 and JNK pathways [85]. Activation of the JAK-STAT pathway by IL6 and IFNG, was suppressed by pretreatment with quercetin and the effects involved STAT1 and STAT3 [73].…”