(+)-Aeroplysinin-1 Modulates the Redox Balance of Endothelial Cells

Abstract

The bioactive natural compound from marine origin, (+)-aeroplysinin-1, has been shown to exhibit potent anti-inflammatory and anti-angiogenic effects. The aim of the present study was to identify new targets for (+)-aeroplysinin-1 in endothelial cells. The sequential use of 2D-electrophoresis and MALDI-TOF-TOF/MS allowed us to identify several differentially expressed proteins. Four of these proteins were involved in redox processes and were validated by Western blot. The effects of (+)-aeroplysinin-1 were further studied by testing the effects of the treatment with this compound on the activity of several anti- and pro-oxidant enzymes, as well as on transcription factors involved in redox homeostasis. Finally, changes in the levels of total reactive oxygen species and mitochondrial membrane potential induced by endothelial cell treatments with (+)-aeroplysinin-1 were also determined. Taken altogether, these findings show that (+)-aeroplysinin-1 has multiple targets involved in endothelial cell redox regulation.

The Antileukemic and Anti-Prostatic Effect of Aeroplysinin-1 Is Mediated through ROS-Induced Apoptosis via NOX Activation and Inhibition of HIF-1a Activity

“…The generation of ROS is mainly derived from complexes I and III of the mitochondrial electron transport chain or from the nicotinamide adenine dinucleotide phosphate NADPH oxidase family on the membrane, which affects the membrane permeability, resulting in mitochondria-mediated apoptosis [ 59 , 60 ]. Previous studies observed that Apl-1 could inhibit the peroxidase NADPH oxidase and activate superoxide dismutase (SOD) to regulate the oxidative balance of endothelial cells, but it did not affect the catalase activity [ 61 ]. To understand whether Apl-1 affects the oxidative balance of leukemia and prostate cancer cells, flow cytometry dye dihydroethidium (DHE) was used to evaluate reactive oxygen species generation in cancer cells.…”

“…Interestingly, previous reports showed that Apl-1 (20 μM) reduced the ROS content in RF-24 endothelial cells [ 61 ]. In this study, it was found that Apl-1 increased the accumulation of ROS in prostate cancer and leukemia cells ( Figure 4 a).…”

“…This led to different results reporting the accumulation of ROS in cells: Apl-1 may cause superoxide accumulation in cells, but not H 2 O 2 superoxide accumulation. The treatment of RF-24 endothelial cells with Apl-1 inhibited NADPH oxidase activity and significantly increased SOD activity, but did not show any relevant effect on catalase [ 61 ]. Our results indicated that Apl-1 treatment activated the protein expression of NOX4 and NOX2 in prostate cancer cells PC-3 and Du145, respectively ( Figure 4 b).…”

Exploring the Diversity of the Marine Environment for New Anti-cancer Compounds

“…Moreover, factors secreted by immune cells can increase mutation rates in cancer cells, thus enabling cancer cells to take on characteristics of other hallmarks (Grivennikov et al, 2010). Aeroplysinin-1 has the potential to inhibit inflammation by decreasing the levels of total reactive oxygen species (Garcia-Vilas et al, 2018), which may make this compound a promising agent to reduce the tumor-promoting effects of inflammation.…”

Control of tumor angiogenesis and metastasis through modulation of cell redox state

“…Peroxyredoxin 2 (Prdx2) helps in the formation of vascular patterns in colon cancer cells HCT116 by vascular mimicry through the activation of VEGFR2, which is suppressed when siPrdx2 is used [116]. On the other hand, endothelial cells treated with the anti-angiogenic compound (+)-aeroplysinin-1 have increased protein levels of Prdx4 [114].…”