β‐Escin sodium inhibits inducible nitric oxide synthase expression via downregulation of the JAK/STAT pathway in A549 cells

Abstract

β-escin, a triterpene saponin, is one of the major active compounds extracted from horse chestnut (Aesculus hippocastanum) seed. Previous work has found that β-escin sodium has antiinflammatory and antitumor effects. In the present study, we investigated its effect on cell proliferation and inducible nitric-oxide synthase (iNOS) expression in human lung carcinoma A549 cells. β-escin sodium (5-40 µg/mL) inhibited cytokine mixture (CM)-induced nitric oxide (NO) production in A549 cells by reducing the expression of iNOS. β-escin sodium suppressed phosphorylation and nuclear translocation of STAT1 (Tyr701) and STAT3 (Tyr705) induced by CM but did not affect the activation of c-Jun and NF-κB. β-escin sodium inhibited the activation of protein tyrosine kinase JAK2. Pervanadate treatment reversed the β-escin sodium-induced downregulation of STAT3 and STAT1. β-escin sodium treatment enhanced an activating phosphorylation of the phosphatase SHP2. Small interfering RNA-mediated knockdown of SHP2 inhibited β-escin sodium-induced phospho-STAT dephosphorylation. Moreover β-escin sodium reduced the activation of p38 MAPK. Finally, β-escin sodium inhibited the proliferation of A549 cells, did not change the cell membrane's permeability, nuclear morphology and size and the mitochondria's transmembrane potential of A549 cells. Taken together, these results demonstrate that β-escin sodium could downregulate iNOS expression through inhibiting JAK/STAT signaling and p38 MAPK activation in A549 cells. β-escin sodium has a marked antiproliferative effect on A549 cells at least in part by inhibiting the JAK/STAT signaling pathway, but not by a cytotoxic effect. β-escin sodium would be useful as a chemopreventive agent or a therapeutic against inflammatory-associated tumor. © 2011 Wiley Periodicals, Inc.

β-Escin Inhibits NNK-Induced Lung Adenocarcinoma and ALDH1A1 and RhoA/Rock Expression in A/J Mice and Growth of H460 Human Lung Cancer Cells

“…This study is consistent with the earlier observations that support possible antitumorigenic effects of b-escin in in vitro and in vivo models (6)(7)(8)(9)(10). Previously, we showed that b-escin, at 250 and 500 ppm in the diet, inhibited colon carcinogen-induced preneoplastic foci in rat colon in a dose-dependent manner (6).…”

Escin augments the efficacy of gemcitabine through down-regulation of nuclear factor-κB and nuclear factor-κB-regulated gene products in pancreatic cancer both in vitro and in vivo

“…Escin has been reported to exhibit antitumor eVects in various cancer cells and synergize with paclitaxel and doxorubicin in human hepatocellular carcinoma cells (Tan et al 2010;Patlolla et al 2006;Ji et al 2011;Zhou et al 2009;Shen et al 2011;Ming et al 2010). However, the eVect of escin against human pancreatic cancer cells is not known.…”

“…1), a natural mixture of triterpene saponins isolated from Aesculus wilsonii Rehd, has been demonstrated to possess anti-cancer activity by the induction of growth inhibition and apoptosis in many human cancer cells in recent years (Tan et al 2010;Patlolla et al 2006;Ji et al 2011;Zhou et al 2009;Shen et al 2011). Another recent study indicated that escin could inhibit proliferation and substantially enhance cytotoxicity of paclitaxel and doxorubicin in human hepatocellular carcinoma cells by down-regulating Cyclin D1, Bcl-2, Bcl-xL, Survivin, Mcl-1 and VEGF (Ming et al 2010).…”

Anti-inflammatory and Anti-cancer Properties of β-Escin, a Triterpene Saponin

“…Shen et al [23] reported that treatment of human cholangiocarcinoma cell lines QBC939, Sk-ChA-1, and MZ-ChA-1 with β-escin induces growth arrest and increases apoptosis with collapse of the mitochondrial membrane potential and the activation of the caspase-3 pathway. Ji et al [24] showed that β-escin inhibits nitric oxide (NO) production and growth of A549 human lung cancer cells by suppressing the JAK/STAT/inducible nitric oxide (iNOS) signaling pathway. Wang et al [25•] revealed that β-escin can potentiate the anti-cancer effect of gemcitabine in pancreatic cancer cell lines.…”