Department of Pharmacology, Faculty of Medicine, and Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, 40002, Thailand.
Phytother Res. 2014 Jun;28(6):841-8. doi: 10.1002/ptr.5061. Epub 2013 Aug 30.
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.
槲皮素和表没食子儿茶素没食子酸酯（EGCG）是具有抗炎和抗肿瘤作用的膳食植物化学物质。在本研究中，我们研究了这两种化合物对胆管癌（CCA）细胞中 Janus 样激酶（JAK）/信号转导和转录（STAT）通路的影响，因为 CCA 是一种侵袭性癌症，预后非常差，而 JAK/STAT 通路在炎症和癌变中起着至关重要的作用。结果表明，促炎细胞因子白细胞介素 6 和干扰素 γ 激活 CCA 细胞中的 JAK/STAT 通路，可被槲皮素和 EGCG 预处理所抑制，明显地通过剂量依赖性降低升高的磷酸化 STAT1 和 STAT3 蛋白。细胞因子介导的 JAK/STAT 级联诱导一氧化氮合酶（iNOS）和细胞间黏附分子 1（ICAM-1）的上调，可被槲皮素和 EGCG 预处理所阻断。此外，这些类黄酮还可以抑制 CCA 细胞的生长和细胞因子诱导的迁移。用特异性 JAK 抑制剂 AG490 和白藜芦醇预处理可消除细胞因子诱导的 iNOS 和 ICAM-1 表达。这些结果表明，槲皮素和 EGCG 对 CCA 细胞 JAK/STAT 级联的抑制具有有益作用。槲皮素和 EGCG 可能作为预防 CCA 的癌症化学预防剂具有潜在用途。
