Enhancement of Antiangiogenic Efficacy of Iron(II) Complex by Selenium Substitution

Abstract

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) (ClO ) (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.

Selenadiazole Derivatives Inhibit Angiogenesis‐Mediated Human Breast Tumor Growth by Suppressing the VEGFR2‐Mediated ERK and AKT Signaling Pathways

“…Compound 1 a inhibition of HUVEC migration, invasion, and structure tube formation were measured as previously described …”

Simple Aggregation‐Induced Emission‐Based Multifunctional Fluorescent Dots for Cancer Therapy In Vitro

“…Af low cytometric analysisw as performed to obtain cell cycle distribution for determiningt he factors that TPAPP-CHO NPs induced cell death. [36] As shown in Figure 4a, the U87 cells that were treated with TPAPP-CHON Ps for7 2h exhibitedaslight accumulationo fc ells in sub-G1p hase, from 2.6 %t o3 1.9 %, indicating that apoptosis wast he main cause of cell death.R eactive oxygen species (ROS) overproduction and the downstream cellular eventsh ave been reported to play important roles in the anticancer actions. Therefore, we also examined the ROS level in U87 cells after treatmentw ith differentc oncentrations of TPAPP-CHO NPs by using dihydroe-thidium (DHE) as af luorescent probe.A si llustrated in the Figure 4b,i ntracellularROS levelsgradually increased from 30 min to 120 min after treatment with TPAPP-CHO NPs, indicating that TPAPP-CHO NPs effectively inducet he intracellular ROS overproduction in cancerc ells.…”

“…As shown in Table S1, we found that the TPAPP‐CHO NPs display significant anticancer activities against a range of cancer cells, such as A375, U87 and U251 cells with IC 50 value of 14.2, 10.1 and 20.9 μ m respectively, while low cytotoxicity towards CHEM‐5 normal cells (IC 50 =24.3 μ m ). A flow cytometric analysis was performed to obtain cell cycle distribution for determining the factors that TPAPP‐CHO NPs induced cell death . As shown in Figure a, the U87 cells that were treated with TPAPP‐CHO NPs for 72 h exhibited a slight accumulation of cells in sub‐G1 phase, from 2.6 % to 31.9 %, indicating that apoptosis was the main cause of cell death.…”

Transferrin-functionalized nanographene oxide for delivery of platinum complexes to enhance cancer-cell selectivity and apoptosis-inducing efficacy

“…34 After 24 hours, the cells were incubated with endocytosis inhibitors for 1 hour, while nystatin (Sigma-Aldrich) was cultured for 30 minutes. Subsequently, the cells were cultured with 20 μM of coumarin-6-loaded Tf-NGO@Pt for 3 hours.…”