Natural compound Byakangelicin suppresses breast tumor growth and motility by regulating SHP-1/JAK2/STAT3 signal pathway

Abstract These authors contributed equally to this work and should be considered co-first authors. Key Points ;Byakangelicin exerts anti-breast cancer effect in vitro. ;Byakangelicin inhibits growth and motility in breast cancer cells. ;Byakangelicin functions via blocking JAK2/STAT3 signal pathway in breast cancer cells. ;Byakangelicin impairs JAK2/STAT3 signal pathway via inducing SHP1. Abstract Byakangelicin is one of the furanocoumarins extracted from the root of Byakangelicin and has protective effect on liver injuryandfibrosis. In addition, Byakangelicin, as a traditional medicine, is also used to treat colds, headache and toothache. Recent studies have shown that Byakangelicin exhibits anti-tumor function; however, the role of Byakangelicin in breast tumor progression and related mechanism has not yet been elucidated. Our study aims to investigate the role of Byakangelicin in breast tumor progression and the underlying mechanism. Methods To measure the effect of Byakangelicin on JAK2/STAT3 signaling, a dual luciferase reporter assay and a western blot assay were performed. CCK8, colony formation, apoptosis and cell invasion assays were used to examine the inhibitory potential of Byakangelicin on breast cancer cells. Additionally, SHP-1 was silenced by specific siRNA duplex and the function of SHP-1 on Byakangelicin-mediated inhibition of JAK2/STAT3 signaling was evaluated. Results Byakangelicin treatment significantly inhibited STAT3 transcriptional activity. In addition, Byakangelicin treatment blocked JAK2/STAT3 signaling in a dose-dependent manner. Byakangelicin-treated tumor cells showed a dramatically reduced proliferation, colony formation and invasion ability. Moreover, Byakangelicin remarkedly induced breast cancer cell apoptosis. Furthermore, Byakangelicin regulated the expression of SHP1. Conclusion In conclusion, our current study indicated that Byakangelicin, a natural compound, inhibits SHP-1/JAK2/STAT3 signaling and thus blocks tumor growth and motility.