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学科主题: 药学
题名:
Bufadienolide compounds sensitize human breast cancer cells to TRAIL-induced apoptosis via inhibition of STAT3/Mcl-1 pathway
作者: Dong, Yinhui1; Yin, Shutao1; Li, Jinghua1; Jiang, Cheng2; Ye, Min3; Hu, Hongbo1
关键词: Bufadienolides ; TRAIL ; Apoptosis ; Breast cancer cells ; Mcl-1
刊名: APOPTOSIS
发表日期: 2011-04-01
DOI: 10.1007/s10495-011-0573-5
卷: 16, 期:4, 页:394-403
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: HEPATOCELLULAR-CARCINOMA ; BUFALIN ; GROWTH ; DEATH ; MECHANISMS ; RESISTANCE ; EXPRESSION ; CHEMOTHERAPY ; INVOLVEMENT ; ACTIVATION
英文摘要:

The death receptor ligand TRAIL is considered a promising candidate for cancer therapy because of its preferential toxicity to malignant cells. However its efficacy has been challenged by a number of resistance mechanisms. Therefore, agents that can overcome the resistance to enhance therapeutic efficacy of TRAIL are needed. In the current study, we found that bufalin, bufotalin and gamabufotalin, key members of bufadienolides isolated from a traditional Chinese medicine ChanSu, significantly potentiated human breast cancer cells with different status of ER-alpha to apoptosis induction of TRAIL, as evidenced by enhanced Annexin V/FITC positive cells (apoptotic cells), cytoplasmic histone-associated-DNA-fragments, membrane permeability transition (MPT), caspases activation and PARP cleavage. Further mechanistic investigation demonstrated that bufalin was able to significantly decrease Mcl-1 expression and modestly decrease Bcl-XL expression level. Down-regulations of these anti-apoptotic proteins were well correlated with inhibition of transcription factor STAT3 activation. The important consequence of down-regulation Mcl-1 in the enhancement action by combining bufalin with TRAIL was confirmed by either knockdown or overexpression of Mcl-1 approach. Our findings for the first time provided strong evidences that bufadienolide compounds have excellent potential to be developed as a novel class of sensitizers of TRAIL.

语种: 英语
所属项目编号: 2009-2-11 ; 31071533 ; 30972172
项目资助者: Chinese Universities Scientific Fund ; National Natural Science Foundation of China (NSFC)
WOS记录号: WOS:000288954900007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64146
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.China Agr Univ, Div Nutr & Hlth, Coll Food Sci & Nutr Engn, Beijing 100083, Peoples R China
2.Univ Minnesota, Hormel Inst, Austin, MN 55912 USA
3.Peking Univ, Hlth Sci Ctr, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
Dong, Yinhui,Yin, Shutao,Li, Jinghua,et al. Bufadienolide compounds sensitize human breast cancer cells to TRAIL-induced apoptosis via inhibition of STAT3/Mcl-1 pathway[J]. APOPTOSIS,2011,16(4):394-403.
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