Flavokawain A suppresses the malignant progression of neuroblastoma in vitro depending on inactivation of ERK/VEGF/MMPs signaling pathway
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 ca...
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Springer
2024-11-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-024-01568-y |
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| author | Mengyao Dong Gaiqin Li Geng Geng Ming Ming Yongtao Xu |
| author_facet | Mengyao Dong Gaiqin Li Geng Geng Ming Ming Yongtao Xu |
| author_sort | Mengyao Dong |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bed13c2200fa4b5b968cb44440743494 |
| institution | OA Journals |
| issn | 2730-6011 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-bed13c2200fa4b5b968cb444407434942025-08-20T02:22:33ZengSpringerDiscover Oncology2730-60112024-11-0115111210.1007/s12672-024-01568-yFlavokawain A suppresses the malignant progression of neuroblastoma in vitro depending on inactivation of ERK/VEGF/MMPs signaling pathwayMengyao Dong0Gaiqin Li1Geng Geng2Ming Ming3Yongtao Xu4Department of Pediatrics, The Affiliated Taian City Central Hospital of Qingdao UniversityDepartment of Gastroenterology, The Affiliated Taian City Central Hospital of Qingdao UniversityDepartment of Pediatric Surgery, The Affiliated Taian City Central Hospital of Qingdao UniversityDepartment of Pediatric Surgery, The Affiliated Taian City Central Hospital of Qingdao UniversityDepartment of Pediatric Surgery, The Affiliated Taian City Central Hospital of Qingdao UniversityAbstract 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.https://doi.org/10.1007/s12672-024-01568-yFlavokawain AERK/VEGF/MMPs pathwayNeuroblastoma |
| spellingShingle | Mengyao Dong Gaiqin Li Geng Geng Ming Ming Yongtao Xu Flavokawain A suppresses the malignant progression of neuroblastoma in vitro depending on inactivation of ERK/VEGF/MMPs signaling pathway Discover Oncology Flavokawain A ERK/VEGF/MMPs pathway Neuroblastoma |
| title | Flavokawain A suppresses the malignant progression of neuroblastoma in vitro depending on inactivation of ERK/VEGF/MMPs signaling pathway |
| title_full | Flavokawain A suppresses the malignant progression of neuroblastoma in vitro depending on inactivation of ERK/VEGF/MMPs signaling pathway |
| title_fullStr | Flavokawain A suppresses the malignant progression of neuroblastoma in vitro depending on inactivation of ERK/VEGF/MMPs signaling pathway |
| title_full_unstemmed | Flavokawain A suppresses the malignant progression of neuroblastoma in vitro depending on inactivation of ERK/VEGF/MMPs signaling pathway |
| title_short | Flavokawain A suppresses the malignant progression of neuroblastoma in vitro depending on inactivation of ERK/VEGF/MMPs signaling pathway |
| title_sort | flavokawain a suppresses the malignant progression of neuroblastoma in vitro depending on inactivation of erk vegf mmps signaling pathway |
| topic | Flavokawain A ERK/VEGF/MMPs pathway Neuroblastoma |
| url | https://doi.org/10.1007/s12672-024-01568-y |
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