A thioredoxin reductase 1 inhibitor pyrano [3,2-a] phenazine inhibits A549 cells proliferation and migration through the induction of reactive oxygen species production

Background: Thioredoxin reductase 1 (TrxR1) inhibitor, pyrano [3,2-a] phenazine, named CPUL-1, was synthesized with potential Anticancer activity. The aim of the present work was to explore the potential anti-proliferative and anti-metastatic ability of CPUL-1 against A549 Cancer cell lines in vitro.

Methods and results: First, Cell Counting Kit-8 (CCK8) assay was used to assess cell proliferation. The A549 cell migration was evaluated by wound healing assay and transwell assay. Second, the epithelial-mesenchymal transition (EMT)-related proteins in A549 cells treated with CPUL-1 were analyzed by western blot methods. Then, TrxR1 Enzyme activity assay and Reactive Oxygen Species (ROS) assay were conducted to evaluate the effect of CPUL-1 on TrxR1 inhibition and ROS levels. Finally, western blotting was used to explore the mechanism of CPUL-1. The study results revealed that the ability of cell proliferation and migration was decreased under CPUL-1 treatment. CPUL-1 could distinctly restrain the migration and invasion of A549 cells through inhibiting EMT process. The results of TrxR1 Enzyme activity assay, ROS assay and western blotting showed that CPUL-1 influenced EMT via inducing ROS-mediated ERK/JNK signaling by inhibiting TrxR1 Enzyme activity.

Conclusions: Together, proliferation suppression and anti-metastasis activity of CPUL-1 in A549 cells were demonstrated by all the evidence. Our findings highlight the great potential of phenazine compound CPUL-1 to suppress A549 cells proliferation and metastasis.

A549; Anti-metastasis; EMT; Phenazine; ROS; TrxR1.