Quantitative Chemical Proteomics Reveals Resveratrol Inhibition of A549 Cell Migration Through Binding Multiple Targets to Regulate Cytoskeleton Remodeling and Suppress EMT

Abstract BackgroundResveratrol (RSV), a cancer chemopreventive natural product, has been shown to affect various cellular processes in tumor cells. However, RSV’s specific protein targets as well as its mechanism of action (MOA) of anticancer effect remain elusive. Recently, quantitative chemical proteomics approach has been an effective tool to identify target proteins, elucidate MOA and predict side effects for active small molecules, especially for natural products.MethodsThe pharmacological activity of RSV was evaluated in A549 cell lines, including the effects on cell proliferation and migration. To elucidate the underlying mechanism, a quantitative chemical proteomics approach was employed to identify the protein targets of RSV. With subsequent in vitro and in vivo experiments, RSV-related pathways and cellular processes were predicted and validated.ResultsRSV significantly inhibited A549 cell migration, but did not affect cell viability. With chemical proteomics approach, 38 target proteins were identified, and proteomic analysis showed that the targets were mainly involved in cytoskeleton remodeling and EMT, which were verified by subsequent in vitro and in vivo assays.ConclusionsRSV inhibits A549 cell migration through binding multiple targets to regulate cytoskeleton remodeling and suppress EMT.