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Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species-mediated apoptosis by targeting the electron transport chain

文献类型：期刊论文

作者Pan, Lijia8,9; Nie, Litong6,7; Yao, Sheng6; Bi, Aiwei4,5; Ye, Yang3,4,5,6; Wu, Yeming2,8,9; Tan, Zhen1,4,5; Wu, Zhixiang4,5,8,9
刊名INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
出版日期2020-12-01
卷号46期号:6页码:2137-2149
ISSN号1107-3756
关键词neuroblastoma bufalin chemical proteomics ETC mitochondria
DOI10.3892/ijmm.2020.4745
通讯作者Tan, Zhen(tanz2008@126.com) ; Wu, Zhixiang(wuzhixiang@xinhuamed.com.cn)
英文摘要The prognosis of high-risk neuroblastoma remains poor. Clinical first-line drugs for treating neuroblastoma have been developed over the previous half-century; however, progress in the identification of new drugs with high efficiency is required. Bufalin, one of the major components of extracts obtained from the venom of the Chinese toad Bufo gargarizans, which is used to treat heart failure in Asian Pacific countries, has been reported to be a potential drug against multiple types of tumor; however, the detailed mechanisms underlying its antitumor activities remain unclear, largely due to lack of knowledge regarding its targets. In the present study, bufalin was revealed to exhibit potent antitumor effects against neuroblastoma, both in vitro and in vivo, using cell proliferation, colony formation, Transwell migration and flow cytometry assays, as well as a nude mouse subcutaneous xenograft model. Moreover, a chemically modified bufalin probe was designed to identify the potential targets of bufalin in neuroblastoma via chemical proteomics. With this strategy, it was revealed that the electron transport chain (ETC) on the inner membrane of mitochondria may contain potential targets for bufalin, and that bufalin-induced mitochondrial-dependent apoptosis may be caused by disruption of the ETC. Collectively, the present study suggests that bufalin may a promising drug for chemotherapy against neuroblastoma, and provides a foundation for further studies into the antitumor mechanisms of bufalin.
WOS关键词DNA-DAMAGE ; CELL-CYCLE ; POLYMERIC PRODRUG ; CANCER CELLS ; IN-VITRO ; PROLIFERATION ; AUTOPHAGY ; GLIOBLASTOMA ; COMBINATION ; ASSOCIATION
资助项目Suzhou Clinical Medicine Innovation Team Introduction Project[SZYJTD201706] ; Natural Science Foundation of China[81874234]
WOS研究方向Research & Experimental Medicine
语种英语
出版者SPANDIDOS PUBL LTD
WOS记录号WOS:000591376800018
源URL[http://119.78.100.183/handle/2S10ELR8/292697]  
专题新药研究国家重点实验室
通讯作者Tan, Zhen; Wu, Zhixiang
作者单位1.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Pediat Hematol Oncol, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China
2.Soochow Univ, Childrens Hosp, Dept Pediat Surg, Suzhou 215003, Jiangsu, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res & Nat Prod, Chem Dept, Shanghai 201203, Peoples R China
7.Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA
8.Shanghai Inst Pediat Res, Div Pediat Oncol, Shanghai 200092, Peoples R China
9.Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Pediat Surg, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China
推荐引用方式
GB/T 7714		 Pan, Lijia,Nie, Litong,Yao, Sheng,et al. Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species-mediated apoptosis by targeting the electron transport chain[J]. INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,2020,46(6):2137-2149.
APA Pan, Lijia.,Nie, Litong.,Yao, Sheng.,Bi, Aiwei.,Ye, Yang.,...&Wu, Zhixiang.(2020).Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species-mediated apoptosis by targeting the electron transport chain.INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,46(6),2137-2149.
MLA Pan, Lijia,et al."Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species-mediated apoptosis by targeting the electron transport chain".INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 46.6(2020):2137-2149.

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来源：上海药物研究所

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