Flavokawain A suppresses the malignant progression of neuroblastoma in vitro depending on inactivation of ERK/VEGF/MMPs signaling pathway
Year: 2024
Type: book-chapter
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.
Source: Discover Oncology
Authors: Mengyao Dong, Gaiqin Li, Geng Geng, Ming Ming, Yongtao Xu
Institutions: Qingdao University, Taian City Central Hospital
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,590
OpenAlex ID: W4404512845