Sinapine Thiocyanate Inhibits the Proliferation and Mobility of Pancreatic Cancer Cells by Up-Regulating GADD45A

Background: Sinapine thiocyanate (ST), an alkaloid isolated from the seeds of cruciferous species, has exhibited anti-inflammatory, anti-malignancy, and anti-angiogenic effects in previous studies. However, the effects and molecular mechanisms of action of ST in pancreatic Cancer (PC) are still limited. Materials and methods: PC cells were treated with different concentrations (0, 20, 40, and 80 μM) of ST. The proliferative ability of PC cells in vitro was determined using cell count kit-8 (CCK-8), 5-ethynyl-2' deoxyuridine, colony formation, and flow cytometry assays. The mobility of PC cells in vitro was analyzed using wound healing assay, transwell assay, Western blotting, and immunofluorescence. High-throughput Sequencing followed by bioinformatics analysis, reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), and Western blotting were performed to identify the key targets of ST. Finally, CCK-8 assay, wound healing assay, and xenograft tumor model were used to determine the relationship between ST and growth arrest and DNA damage-inducible alpha (GADD45A; the key target of ST) and malignant biological properties of PC in vitro and in vivo. Results: ST significantly repressed the PC cell proliferation rate and colony formation in vitro and arrested cells in the G2/M phase. ST inhibited PC cell mobility in vitro and increased E-cadherin expression (an epithelial biomarker). GADD45A was considered the key target of ST in PC and was elevated in PC cells treated with ST. The inhibition of GADD45A significantly alleviated the suppressive effects of ST on PC cell proliferation and mobility in vitro. ST suppressed PC cell proliferation in vivo and increased GADD45A expression in tumor tissues. Conclusion: ST exhibited significant anti-tumor effects on PC cells by upregulating GADD45A. ST may be a potential drug for PC treatment.