Esculentoside H inhibits colon cancer cell migration and growth through suppression of MMP‐9 gene expression via NF‐kB signaling pathway

信号转导 蛋白激酶C 细胞迁移 下调和上调 NF-κB 佛波 p38丝裂原活化蛋白激酶 磷酸化 细胞生长 化学 基质金属蛋白酶 激酶 癌症研究 癌细胞 分子生物学 αBκ 细胞生物学 细胞 生物 癌症 MAPK/ERK通路 内科学 医学 生物化学 基因
作者
Sun-Hyung Ha,Kyung-Min Kwon,Jun-Young Park,Fukushi Abekura,Young Choon Lee,Tae‐Wook Chung,Ki‐Tae Ha,Hyeun Wook Chang,Seung-Hak Cho,Jong‐Suk Kim,Cheorl-Ho Kim
出处
期刊:Journal of Cellular Biochemistry [Wiley]
卷期号:120 (6): 9810-9819 被引量:22
标识
DOI:10.1002/jcb.28261
摘要

Abstract A water‐soluble saponin, Esculentoside H (EsH), 3‐ O ‐( O ‐β‐ d ‐glucopyranosyl‐(1→4)‐β‐ d ‐xylopyranosyl)‐28‐β‐ d ‐glucopyranosylphytolaccagenin has been isolated and purified from the root extract of perennial plant Phytolacca esculenta . EsH is known to be an anticancer compound, having a capacity for TNF‐α release. However, the effects of EsH on migration and growth in tumor cells have not yet been reported. In the current study, the suppressive effects of EsH on phorbol 12‐myristate 13‐acetate (PMA)‐induced cell migration were examined in murine colon cancer CT26 cells and human colon cancer HCT116 cells. Interestingly, the transwell assay and wound healing show that EsH suppresses the PMA‐induced migration and growth potential of HCT116 and CT26 colon cancer cells, respectively. EsH dose‐dependently suppressed matrix metalloproteinases‐9 (MMP‐9) expression that was upregulated upon PMA treatment in messenger RNA levels and protein secretion. Since the expression of MMP‐9 is correlated with nuclear factor‐κB (NF‐κB) signaling, it has been examined whether EsH inhibits PMA‐induced IκB phosphorylation that leads to the suppression of NK‐κB nuclear translocation. EsH repressed the phosphorylation level of JNK, but not extracellular signal‐regulated kinase and p38 signaling when the cells were treated with PMA. Overall, these results demonstrated that EsH could suppress cancer migration through blockage of the JNK1/2 and NF‐κB signaling‐mediated MMP‐9 expression.
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