Qifan Ding1, Hengyu Wang1, Ying Wang2, Yuanyuan Lu3. 1. Department of Marine Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. 2. Department of Marine Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. cpuwangying@126.com. 3. Department of Marine Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. luyy@cpu.edu.cn.
Abstract
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.
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.
Authors: Michael Poullis; Michael Shackcloth; Richard Page; Julius Asanti-Siaw; Steven Woolley; Neeraj Mediratta Journal: Asian Cardiovasc Thorac Ann Date: 2014-08-07