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Luteoloside Induces G0/G1 Phase Arrest of Neuroblastoma Cells by Targeting p38 MAPK
Ya He1, Maohong Luo1, Shan Lei1
1Guizhou 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.
Abstract:
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.
Insights
Luteoloside effectively inhibits neuroblastoma cell proliferation in vitro and in vivo. This natural compound activates the p38 MAPK pathway, showing potential as an anticancer drug for neuroblastoma treatment.
Area of Science:
- Pharmacology
- Oncology
- Molecular Biology
Background:
- Luteoloside exhibits anti-inflammatory, antiviral, and antitumor properties.
- The specific effects and mechanisms of luteoloside on neuroblastoma remain uninvestigated.
Purpose of the Study:
- To investigate the anti-neuroblastoma effects of luteoloside.
- To elucidate the underlying molecular mechanisms, focusing on the p38 MAPK pathway.
Main Methods:
- In vitro assays (MTT, colony formation, Hoechst staining, flow cytometry) on neuroblastoma cell lines (SH-SY5Y, SK-N-AS).
- In vivo studies using a subcutaneous tumorigenesis model in nude mice.
- Bioinformatics, molecular docking, cellular thermal shift assays, and p38 MAPK inhibition (SB203580) to identify and validate targets.
Main Results:
- Luteoloside significantly inhibited neuroblastoma cell proliferation both in vitro and in vivo.
- Luteoloside induced G0/G1 phase arrest and downregulated cell cycle-related genes and proteins (cyclin D1, CDK4, C-myc).
- p38 MAPK was identified as a direct target of luteoloside, and its inhibition reversed the anti-proliferative effects.
Conclusions:
- Luteoloside demonstrates potent anti-neuroblastoma activity.
- The mechanism involves the activation of the p38 MAPK pathway.
- Luteoloside represents a promising therapeutic candidate for neuroblastoma treatment.
