Luteoloside Induces G0/G1 Phase Arrest of Neuroblastoma Cells by Targeting p38 MAPK
Ya He,
Maohong Luo,
Shan Lei,
Zhirui Zeng,
Tengxiang Chen,
Yingmin Wu,
Dongyan Wang,
Long Wang,
Lu Wang
Affiliations
Ya He
Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Disease, Department of Physiology, College of Basic Medicine, Guizhou Medical University, Guiyang 550025, China
Maohong Luo
Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Disease, Department of Physiology, College of Basic Medicine, Guizhou Medical University, Guiyang 550025, China
Shan Lei
Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Disease, Department of Physiology, College of Basic Medicine, Guizhou Medical University, Guiyang 550025, China
Zhirui Zeng
Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Disease, Department of Physiology, College of Basic Medicine, Guizhou Medical University, Guiyang 550025, China
Tengxiang Chen
Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Disease, Department of Physiology, College of Basic Medicine, Guizhou Medical University, Guiyang 550025, China
Yingmin Wu
Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Disease, Department of Physiology, College of Basic Medicine, Guizhou Medical University, Guiyang 550025, China
Dongyan Wang
Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Disease, Department of Physiology, College of Basic Medicine, Guizhou Medical University, Guiyang 550025, China
Long Wang
Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Disease, Department of Physiology, College of Basic Medicine, Guizhou Medical University, Guiyang 550025, China
Lu Wang
Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Disease, Department of Physiology, College of Basic Medicine, Guizhou Medical University, Guiyang 550025, China
Luteoloside has shown anti-inflammatory, antiviral, and antitumor properties. However, the effect and mechanism of luteoloside on neuroblastoma cells remain unknown. The proliferation of human neuroblastoma cells (SH-SY5Y and SK-N-AS) treated with different concentrations of luteoloside (0, 12.5, 25, and 50 μM) was detected by the MTT assay and colony formation assay. Cell apoptosis and cell cycle were examined by Hoechst staining and flow cytometry. A subcutaneous tumorigenesis model was established in nude mice to evaluate the effect of luteoloside on tumor growth in vivo. Bioinformatics, molecular docking techniques, and cellular thermal shift assays were utilized to predict the potential targets of luteoloside in neuroblastoma. The p38 MAPK inhibitor SB203580 was used to confirm the role of p38 MAPK. Luteoloside inhibited the proliferation of neuroblastoma cells in vitro and in vivo. Luteoloside slightly induced cellular G0/G1 phase arrest and reduced the expression levels of G0/G1 phase–related genes and the proteins cyclin D1, CDK4, and C-myc, which are downregulated by p38 MAPK pathways. Meanwhile, p38 was identified as the target of luteoloside, and inhibition of p38 MAPK reversed the inhibitory effect of luteoloside on neuroblastoma cells. Luteoloside is a potential anticancer drug for treating neuroblastoma by activating p38 MAPK.
