Compound K Induces Endoplasmic Reticulum Stress and Apoptosis in Human Liver Cancer Cells by Regulating STAT3.
Compound K Induces Endoplasmic Reticulum Stress and Apoptosis in Human Liver Cancer Cells by Regulating STAT3.
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化合物 K 通过调节 STAT3 诱导人肝癌细胞内质网应激和细胞凋亡
DOI：
10.3390/molecules23061482
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发表时间：
2018-06-19
期刊：
影响因子：
--
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Zhang X;Zhang S;Sun Q;Jiao W;Yan Y;Zhang X
人参皂苷K（20-O-β-d-glucopyranosyl-20（S）-protopanaxadiol; CK）是人参原人参二醇皂苷的肠道细菌代谢物，据报道其可诱导许多癌细胞凋亡;然而，其在人肝细胞癌（HCC）细胞中的活性的确切机制尚不清楚。在此，我们证明CK抑制HepG 2和SMMC-7721细胞的生长和集落形成，通过诱导凋亡介导的表型。CK对正常肝癌细胞的毒性较低。CK处理HepG 2和SMMC-7721细胞后，p-STAT 3水平降低，未折叠蛋白反应的三个分支被激活，内质网应激（ERS）相关蛋白水平升高。我们还发现，CK降低STAT 3的DNA结合能力。此外，通过CRISPR/Cas9技术沉默STAT 3增强了CK诱导的ERS和凋亡。最后，我们发现CK抑制肝癌异种移植物的生长，毒性很小。用CK处理的携带人HCC异种移植物的小鼠显示GRP 78表达增加和p-STAT 3水平降低。综上所述，这些数据表明CK通过抑制人肝癌细胞中的p-STAT 3而诱导ERS和凋亡;因此，CK可能是人HCC的潜在治疗候选物。
The ginsenoside compound K (20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol; CK) is an intestinal bacterial metabolite of ginseng protopanaxadiol saponin that has been reported to induce apoptosis in many cancer cells; however, the precise mechanisms of its activity in human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we demonstrated that CK inhibited the growth and colony formation of HepG2 and SMMC-7721 cells, phenotypes that were mediated by inducing apoptosis. Meanwhile, CK showed lower toxicity in normal hepatoma cells. After treating HepG2 and SMMC-7721 cells with CK, p-STAT3 levels decreased, the three branches of the unfolded protein response were activated, and levels of endoplasmic reticulum stress (ERS)-related proteins were increased. We also revealed that CK decreased the DNA-binding capacity of STAT3. Moreover, silencing STAT3 with CRISPR/Cas9 technology enhanced CK-induced ERS and apoptosis. Finally, we showed that CK inhibited the growth of liver cancer xenografts with little toxicity. Mice bearing human HCC xenografts that were treated with CK showed increased GRP78 expression and decreased p-STAT3 levels. Taken together, these data showed that CK induced ERS and apoptosis by inhibiting p-STAT3 in human liver cancer cells; thus, CK might be a potential therapeutic candidate for human HCC.
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影响因子：
7.8
作者：
Hitomi, Junichi;Katayama, Taiichi;Eguchi, Yutaka;Kudo, Takashi;Taniguchi, Manabu;Koyama, Yoshihisa;Manabe, Takayuki;Yamagishi, Satoru;Bando, Yoshio;Imaizumi, Kazunori;Tsujimoto, Yoshihide;Tohyama, Masaya
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Tohyama, Masaya
影响因子：
11.4
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Iuliano L
影响因子：
8.2
作者：
Shi, Jing;Xue, Wei;Li, Ke-xin
通讯作者：
Li, Ke-xin
影响因子：
9.7
作者：
Lee, SJ;Sung, JH;Lee, BH
通讯作者：
Lee, BH
影响因子：
6.4
作者：
Banerjee K;Resat H
通讯作者：
Resat H