Nuciferine inhibits the progression of glioblastoma by suppressing the SOX2-AKT/STAT3-Slug signaling pathway
Abstract Background Nuciferine (NF), extracted from the leaves of N. nucifera Gaertn, has been shown to exhibit anti-tumor and anti-viral pharmacological properties. It can also penetrate the blood brain barrier (BBB). However, the mechanism by which NF inhibits glioblastoma (GBM) progression is not...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1134-y |
| _version_ | 1819049308345860096 |
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| author | Zizhuo Li Yaodong Chen Tingting An Pengfei Liu Jiyuan Zhu Haichao Yang Wei Zhang Tianxiu Dong Jian Jiang Yu Zhang Maitao Jiang Xiuhua Yang |
| author_facet | Zizhuo Li Yaodong Chen Tingting An Pengfei Liu Jiyuan Zhu Haichao Yang Wei Zhang Tianxiu Dong Jian Jiang Yu Zhang Maitao Jiang Xiuhua Yang |
| author_sort | Zizhuo Li |
| collection | DOAJ |
| description | Abstract Background Nuciferine (NF), extracted from the leaves of N. nucifera Gaertn, has been shown to exhibit anti-tumor and anti-viral pharmacological properties. It can also penetrate the blood brain barrier (BBB). However, the mechanism by which NF inhibits glioblastoma (GBM) progression is not well understood. We aimed to determine the anti-tumor effect of NF on GBM cell lines and clarify the potential molecular mechanism involved. Methods U87MG and U251 cell lines were used in vitro to assess the anti-tumor efficacy of NF. Cytotoxicity, viability, and proliferation were evaluated by MTT and colony formation assay. After Annexin V-FITC and PI staining, flow cytometry was performed to evaluate apoptosis and cell cycle changes in NF-treated GBM cells. Wound healing and Transwell assays were used to assess migration and invasion of GBM cells. Western blot analysis, immunofluorescence staining, immunohistochemistry, and bioinformatics were used to gain insights into the molecular mechanisms. Preclinical therapeutic efficacy was mainly estimated by ultrasound and MRI in xenograft nude mouse models. Results NF inhibited the proliferation, mobility, stemness, angiogenesis, and epithelial-to-mesenchymal transition (EMT) of GBM cells. Additionally, NF induced apoptosis and G2 cell cycle arrest. Slug expression was also decreased by NF via the AKT and STAT3 signaling pathways. Interestingly, we discovered that NF affected GBM cells partly by targeting SOX2, which may be upstream of the AKT and STAT3 pathways. Finally, NF led to significant tumor control in GBM xenograft models. Conclusions NF inhibited the progression of GBM via the SOX2-AKT/STAT3-Slug signaling pathway. SOX2-targeting with NF may offer a novel therapeutic approach for GBM treatment. |
| first_indexed | 2024-12-21T11:30:05Z |
| format | Article |
| id | doaj.art-e6cfa8ab0de24a0cb10286e60e293941 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-21T11:30:05Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-e6cfa8ab0de24a0cb10286e60e2939412022-12-21T19:05:35ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-03-0138111510.1186/s13046-019-1134-yNuciferine inhibits the progression of glioblastoma by suppressing the SOX2-AKT/STAT3-Slug signaling pathwayZizhuo Li0Yaodong Chen1Tingting An2Pengfei Liu3Jiyuan Zhu4Haichao Yang5Wei Zhang6Tianxiu Dong7Jian Jiang8Yu Zhang9Maitao Jiang10Xiuhua Yang11Department of Abdominal Ultrasound, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Abdominal Ultrasound, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Abdominal Ultrasound, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Magnetic Resonance, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Pathology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Abdominal Ultrasound, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Abdominal Ultrasound, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Abdominal Ultrasound, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Abdominal Ultrasound, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Abdominal Ultrasound, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Abdominal Ultrasound, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Abdominal Ultrasound, The First Affiliated Hospital of Harbin Medical UniversityAbstract Background Nuciferine (NF), extracted from the leaves of N. nucifera Gaertn, has been shown to exhibit anti-tumor and anti-viral pharmacological properties. It can also penetrate the blood brain barrier (BBB). However, the mechanism by which NF inhibits glioblastoma (GBM) progression is not well understood. We aimed to determine the anti-tumor effect of NF on GBM cell lines and clarify the potential molecular mechanism involved. Methods U87MG and U251 cell lines were used in vitro to assess the anti-tumor efficacy of NF. Cytotoxicity, viability, and proliferation were evaluated by MTT and colony formation assay. After Annexin V-FITC and PI staining, flow cytometry was performed to evaluate apoptosis and cell cycle changes in NF-treated GBM cells. Wound healing and Transwell assays were used to assess migration and invasion of GBM cells. Western blot analysis, immunofluorescence staining, immunohistochemistry, and bioinformatics were used to gain insights into the molecular mechanisms. Preclinical therapeutic efficacy was mainly estimated by ultrasound and MRI in xenograft nude mouse models. Results NF inhibited the proliferation, mobility, stemness, angiogenesis, and epithelial-to-mesenchymal transition (EMT) of GBM cells. Additionally, NF induced apoptosis and G2 cell cycle arrest. Slug expression was also decreased by NF via the AKT and STAT3 signaling pathways. Interestingly, we discovered that NF affected GBM cells partly by targeting SOX2, which may be upstream of the AKT and STAT3 pathways. Finally, NF led to significant tumor control in GBM xenograft models. Conclusions NF inhibited the progression of GBM via the SOX2-AKT/STAT3-Slug signaling pathway. SOX2-targeting with NF may offer a novel therapeutic approach for GBM treatment.http://link.springer.com/article/10.1186/s13046-019-1134-yNuciferineGlioblastomaSOX2-AKT/STAT3-Slug signaling pathwayEMT |
| spellingShingle | Zizhuo Li Yaodong Chen Tingting An Pengfei Liu Jiyuan Zhu Haichao Yang Wei Zhang Tianxiu Dong Jian Jiang Yu Zhang Maitao Jiang Xiuhua Yang Nuciferine inhibits the progression of glioblastoma by suppressing the SOX2-AKT/STAT3-Slug signaling pathway Journal of Experimental & Clinical Cancer Research Nuciferine Glioblastoma SOX2-AKT/STAT3-Slug signaling pathway EMT |
| title | Nuciferine inhibits the progression of glioblastoma by suppressing the SOX2-AKT/STAT3-Slug signaling pathway |
| title_full | Nuciferine inhibits the progression of glioblastoma by suppressing the SOX2-AKT/STAT3-Slug signaling pathway |
| title_fullStr | Nuciferine inhibits the progression of glioblastoma by suppressing the SOX2-AKT/STAT3-Slug signaling pathway |
| title_full_unstemmed | Nuciferine inhibits the progression of glioblastoma by suppressing the SOX2-AKT/STAT3-Slug signaling pathway |
| title_short | Nuciferine inhibits the progression of glioblastoma by suppressing the SOX2-AKT/STAT3-Slug signaling pathway |
| title_sort | nuciferine inhibits the progression of glioblastoma by suppressing the sox2 akt stat3 slug signaling pathway |
| topic | Nuciferine Glioblastoma SOX2-AKT/STAT3-Slug signaling pathway EMT |
| url | http://link.springer.com/article/10.1186/s13046-019-1134-y |
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