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Ent-11 alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid inhibits hepatocellular carcinoma in vitro and in vivo via stabilizing IkB alpha
Chen, George G.1; Leung, Jackie1; Liang, Nian Ci2; Li, Li2; Wu, Kefeng2; Chan, Ursula P. F.1; Leung, Billy C. S.1; Li, Mingyue1; Du, Jing3; Deng, Yi Feng2; Gong, Xianling2; Lv, Yingnian2; Chak, Ernest C. W.1; Lai, Paul B. S.1
关键词Hepatocellular Carcinoma Ent-11-hydroxy-15-oxo-kaur-16-en-19-oic-acid Apoptosis Toxicity Nuclear Factor-kappab
刊名INVESTIGATIONAL NEW DRUGS
2012-12-01
DOI10.1007/s10637-011-9791-5
30期:6页:2210-2218
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology ; Pharmacology & Pharmacy
研究领域[WOS]Oncology ; Pharmacology & Pharmacy
关键词[WOS]NF-KAPPA-B ; CELL-DEATH ; CANCER CELLS ; LIVER ; APOPTOSIS ; BCL-2 ; EXPRESSION ; PATHWAY ; OVEREXPRESSION ; MICE
英文摘要

Ent-11-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) isolated from Pteris Semipinnata L is known to inhibit certain tumor cells in vitro. The information on the in vivo effect of 5F is limited and its effect on hepatocellular carcinoma (HCC) is unknown. In this study, the anti-tumor effect of 5F was investigated in a diethylnitrosamine (DEN)-induced mouse HCC model. In addition to therapeutic effect, the potential side effect was monitored. A panel of cultured HCC cells was used to confirm the in vivo data and explore the responsible molecular pathway. The result showed that 5F significantly inhibited the DEN-induced HCC tumors by reducing the number of tumor foci and the volume of tumors. Furthermore, 5F induced the death of cultured HCC cells in dose- and time-dependent manners. The cell death was confirmed to be apoptotic by in vivo and in vitro TUNEL assays. 5F inhibited NF-kB by stabilizing its inhibitor IkB alpha, reducing the nuclear p65 and inhibiting NF-kB activity. Subsequently it affected the NF-kB downstream molecules with a decrease in anti-apoptotic Bcl-2 and increase in pro-apoptotic Bax and Bak. During the whole period of the experiment, mice receiving 5F appeared to be healthy, though they suffered from a mild degree of hair loss. 5F did not damage liver and renal functions. In conclusion, 5F is effective against HCC with minimal side effects. It induces apoptosis in HCC cells via inhibiting NF-kB, leading to the decrease of Bcl-2 but the increase of Bax and Bak.

语种英语
WOS记录号WOS:000310470100013
项目编号GHP/022/06
资助机构Innovation and Technology Fund of Innovation and Technology Commission, the government of the Hong Kong Special Administration Region
引用统计
被引频次:9[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53125
专题北京大学深圳医院
作者单位1.Chinese Univ Hong Kong, Prince Wales Hosp, Dept Surg, Shatin, Hong Kong, Peoples R China
2.Guangdong Med Coll, Inst Biochem & Mol Biol, Zhanjiang, Guangdong, Peoples R China
3.Peking Univ, Shenzhen Hosp, Dept Lab Med, Shenzhen, Guangdong, Peoples R China
推荐引用方式
GB/T 7714
Chen, George G.,Leung, Jackie,Liang, Nian Ci,et al. Ent-11 alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid inhibits hepatocellular carcinoma in vitro and in vivo via stabilizing IkB alpha[J]. INVESTIGATIONAL NEW DRUGS,2012,30(6):2210-2218.
APA Chen, George G..,Leung, Jackie.,Liang, Nian Ci.,Li, Li.,Wu, Kefeng.,...&Lai, Paul B. S..(2012).Ent-11 alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid inhibits hepatocellular carcinoma in vitro and in vivo via stabilizing IkB alpha.INVESTIGATIONAL NEW DRUGS,30(6),2210-2218.
MLA Chen, George G.,et al."Ent-11 alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid inhibits hepatocellular carcinoma in vitro and in vivo via stabilizing IkB alpha".INVESTIGATIONAL NEW DRUGS 30.6(2012):2210-2218.
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