DICP OpenIR
psi-Bufarenogin, a novel anti-tumor compound, suppresses liver cancer growth by inhibiting receptor tyrosine kinase-mediated signaling
Ding, Jin1; Wen, Wen1; Xiang, Daimin1; Yin, Peipei1,2; Liu, Yanfang3; Liu, Chang2; He, Guoping1; Cheng, Zhuo1; Yin, Jianpeng5; Sheng, Chunquan4; Zhang, Wen4; Nan, Fajun5; Ye, Wencai6; Zhang, Xiuli3; Wang, Hongyang1,7
关键词Psi-bufarenogin Hepatocellular Carcinoma Epithelial Growth Factor Receptor Hepatocyte Growth Factor Receptor
刊名ONCOTARGET
2015-05-10
6期:13页:11627-11639
收录类别SCI
文章类型Article
WOS标题词Science & Technology ; Life Sciences & Biomedicine
类目[WOS]Oncology ; Cell Biology
研究领域[WOS]Oncology ; Cell Biology
关键词[WOS]ADVANCED HEPATOCELLULAR-CARCINOMA ; CELL LUNG-CANCER ; STEM-CELLS ; INTERACTION CHROMATOGRAPHY ; APOPTOSIS ; MET ; BUFADIENOLIDES ; IDENTIFICATION ; PROLIFERATION ; ACTIVATION
英文摘要Resistance of hepatocellular carcinoma (HCC) to existing chemotherapeutic agents largely contributes to the poor prognosis of patients, and discovery of novel anti-HCC drug is in an urgent need. Herein we report psi-Bufarenogin, a novel active compound that we isolated from the extract of toad skin, exhibited potent therapeutic effect in xenografted human hepatoma without notable side effects. In vitro, psi-Bufarenogin suppressed HCC cells proliferation through impeding cell cycle progression, and it facilitated cell apoptosis by downregulating Mcl-1 expression. Moreover,psi-Bufarenogin decreased the number of hepatoma stem cells through Sox2 depression and exhibited synergistic effect with conventional chemotherapeutics. Mechanistic study revealed that psi-Bufarenogin impaired the activation of MEK/ERK pathway, which is essential in the proliferation of hepatoma cells. psi-Bufarenogin notably suppressed PI3-K/Akt cascade, which was required in psi-Bufarenogin-mediated reduction of Mcl-1 and Sox2. psi-Bufarenogin inhibited the auto-phosphorylation and activation of epithelial growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-Met), thereafter suppressed their primary downstream cascades Raf/MEK/ERK and PI3-K/Akt signaling. Taken together, psi-Bufarenogin suppressed HCC growth via inhibiting, at least partially, receptor tyrosine kinases-regulated signaling, suggesting that psi-Bufarenogin could be a novel lead compound for anti-HCC drug.
语种英语
WOS记录号WOS:000359006400073
引用统计
被引频次:2[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/146429
专题中国科学院大连化学物理研究所
作者单位1.Second Mil Med Univ, Int Cooperat Lab Signal Transduct, Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China
2.Shanghai Inst Pharmaceut Ind, Dept Pharmacol, Shanghai, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, Dalian, Peoples R China
4.Second Mil Med Univ, Coll Pharm, Shanghai, Peoples R China
5.Natl Ctr Drug Screen, Shanghai, Peoples R China
6.Jinan Univ, Coll Pharm, Guangzhou, Guangdong, Peoples R China
7.Natl Ctr Liver Canc, Shanghai, Peoples R China
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GB/T 7714
Ding, Jin,Wen, Wen,Xiang, Daimin,et al. psi-Bufarenogin, a novel anti-tumor compound, suppresses liver cancer growth by inhibiting receptor tyrosine kinase-mediated signaling[J]. ONCOTARGET,2015,6(13):11627-11639.
APA Ding, Jin.,Wen, Wen.,Xiang, Daimin.,Yin, Peipei.,Liu, Yanfang.,...&Wang, Hongyang.(2015).psi-Bufarenogin, a novel anti-tumor compound, suppresses liver cancer growth by inhibiting receptor tyrosine kinase-mediated signaling.ONCOTARGET,6(13),11627-11639.
MLA Ding, Jin,et al."psi-Bufarenogin, a novel anti-tumor compound, suppresses liver cancer growth by inhibiting receptor tyrosine kinase-mediated signaling".ONCOTARGET 6.13(2015):11627-11639.
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