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Anticancer osmium complex inhibitors of the HIF-1 alpha and p300 protein-protein interaction
Yang, Chao1; Wang, Wanhe2; Li, Guo-Dong1; Zhong, Hai-Jing1; Dong, Zhen-Zhen2; Wong, Chun-Yuen3; Kwong, Daniel W. J.2; Ma, Dik-Lung2; Leung, Chung-Hang1
2017-02-22
Source PublicationSCIENTIFIC REPORTS
ISSN2045-2322
Volume7
Abstract

The hypoxia inducible factor (HIF) pathway has been considered to be an attractive anti-cancer target. One strategy to inhibit HIF activity is through the disruption of the HIF-1 alpha-p300 protein-protein interaction. We report herein the identification of an osmium(II) complex as the first metal-based inhibitor of the HIF-1 alpha-p300 interaction. We evaluated the effect of complex 1 on HIF-1 alpha signaling pathway in vitro and in cellulo by using the dual luciferase reporter assay, co-immunoprecipitation assay, and immunoblot assay. Complex 1 exhibited a dose-dependent inhibition of HRE-driven luciferase activity, with an IC50 value of 1.22 mu M. Complex 1 interfered with the HIF-1 alpha-p300 interaction as revealed by a dose-dependent reduction of p300 co-precipitated with HIF-1 alpha as the concentration of complex 1 was increased. Complex 1 repressed the phosphorylation of SRC, AKT and STAT3, and had no discernible effect on the activity of NF-kappa B. We anticipate that complex 1 could be utilized as a promising scaffold for the further development of more potent HIF-1 alpha inhibitors for anti-cancer treatment.

DOI10.1038/srep42860
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000394759400001
PublisherNATURE PUBLISHING GROUP
The Source to ArticleWOS
Fulltext Access
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Cited Times [WOS]:12   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.University of Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
2.Hong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R China
3.City Univ Hong Kong, Dept Biol & Chem, Tat Chee Ave, Kowloon, Hong Kong, Peoples R China
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Yang, Chao,Wang, Wanhe,Li, Guo-Dong,et al. Anticancer osmium complex inhibitors of the HIF-1 alpha and p300 protein-protein interaction[J]. SCIENTIFIC REPORTS,2017,7.
APA Yang, Chao.,Wang, Wanhe.,Li, Guo-Dong.,Zhong, Hai-Jing.,Dong, Zhen-Zhen.,...&Leung, Chung-Hang.(2017).Anticancer osmium complex inhibitors of the HIF-1 alpha and p300 protein-protein interaction.SCIENTIFIC REPORTS,7.
MLA Yang, Chao,et al."Anticancer osmium complex inhibitors of the HIF-1 alpha and p300 protein-protein interaction".SCIENTIFIC REPORTS 7(2017).
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