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Open Access 01-12-2024 | Research

Flavokawain A suppresses the malignant progression of neuroblastoma in vitro depending on inactivation of ERK/VEGF/MMPs signaling pathway

Authors: Mengyao Dong, Gaiqin Li, Geng Geng, Ming Ming, Yongtao Xu

Published in: Discover Oncology | Issue 1/2024

Abstract

Background

Neuroblastoma (NB), the most common extracranial solid tumor in children, is featured by high malignancy and poor prognosis. Flavokawain A (FKA), a novel chalcone isolated from the roots of the kava plant, has been identified to exert the tumor-inhibiting properties in various cancers. The present study was formulated to tell about the anticarcinogenic effects of FKA against NB and to thoroughly elucidate the intrinsic molecular mechanisms.

Methods

In this work, for functional experiments, SK-N-SH cells were treated with various concentrations (0, 12.5, 25, 50 μM) of FKA in order to expound the tumor-inhibiting functions of FKA on proliferative ability, clone-forming ability, apoptosis, cell cycle arrest, migratory ability, invasive ability, EMT and in vitro angiogenesis of NB cells. Moreover, to probe into the intrinsic molecular mechanisms underlying the tumor-inhibiting functions of FKA in NB cells, FKA-treated SK-N-SH cells were co-treated with ERK activator LM22B-10 for rescue experiments.

Results

In our current work, it was verified that FKA treatment suppressed the proliferative and clone-forming abilities of NB cells, facilitated NB cell apoptosis, arrested NB cell cycle as well as inhibited NB cell migration, invasion, EMT and in vitro angiogenesis in a dose-dependent manner. What’s more, molecular docking predicted the compound-protein interaction between FKA and ERK and biotin pull-down assay validated the binding of FKA to ERK. FKA targeted on ERK and acted as an inhibitor of ERK to inactivate ERK/VEGF/MMPs signaling pathway. Treatment with ERK activator LM22B-10 partially abolished the tumor-inhibiting functions of FKA in NB.

Conclusion

Overall, FKA may suppress the malignant behaviors of NB cells depending on inactivation of ERK/VEGF/MMPs signaling pathway.

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Title: Flavokawain A suppresses the malignant progression of neuroblastoma in vitro depending on inactivation of ERK/VEGF/MMPs signaling pathway
Authors: Mengyao Dong
Gaiqin Li
Geng Geng
Ming Ming
Yongtao Xu
Publication date: 01-12-2024
Publisher: Springer US
Published in: Discover Oncology / Issue 1/2024
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI: https://doi.org/10.1007/s12672-024-01568-y

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Abstract

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