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Enhancement of Antiangiogenic Efficacy of Iron(II) Complex by Selenium Substitution
Author(s) -
Lai Haoqiang,
Zhang Xiang,
Feng Pengju,
Xie Lina,
Chen Jinjin,
Chen Tianfeng
Publication year - 2017
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201700272
Subject(s) - selenium , substitution (logic) , chemistry , medicine , computer science , organic chemistry , programming language
Antiangiogenesis therapy is a proven strategy for the treatment of cancers. Herein, we demonstrate that iron(II) complexes containing 1,10‐phenanthroline(phen) derivatives were capable of suppressing angiogenesis in vitro in a dose‐dependent manner. Interestingly, the introduction of selenium into an iron(II) complex ((Fe(phenSe) 3 (ClO 4 ) 2 (phenSe=2‐selenoimidazole[4,5‐f]1,10‐phenanthroline)) could enhance its antiangiogenic efficacy. Mechanistic studies demonstrated that the complex potently induced endothelial cell apoptosis as evidenced by activation of caspases and PARP cleavage. The iron(II) complex activated p53‐mediated mitochondrial dysfunction as can be seen by the upregulation in the expression of p53 and proapoptotic Bcl‐2 family proteins, and downregulation in the expression of Bcl‐2 family proteins. Additionally, the complex inhibited VEGF expression and gave rise to dephosphorylated AKT, which suppressed the transmission of the mitogenic signaling pathway. Taken together, this study could provide a strategy for the rational design of high‐efficacy antivascular agents.