Deapioplatycodin D inhibits glioblastoma cell proliferation by inducing BNIP3L-mediated incomplete mitophagy
Abstract Deapioplatycodin D (DPD) is a triterpenoid saponin natural compound isolated from the Chinese herb Platycodon grandiflorum that has antiviral and antitumor properties. This study aimed to investigate the effects of DPD on glioblastoma (GBM) cells and to determine its intrinsic mechanism of...
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BMC
2025-01-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03636-x |
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| author | Yu Sun Guangze Zhu Renshuang Zhao Yaru Li Hongyang Li Yunyun Liu Ningyi Jin Xiao Li Yiquan Li Tiemei Liu |
| author_facet | Yu Sun Guangze Zhu Renshuang Zhao Yaru Li Hongyang Li Yunyun Liu Ningyi Jin Xiao Li Yiquan Li Tiemei Liu |
| author_sort | Yu Sun |
| collection | DOAJ |
| description | Abstract Deapioplatycodin D (DPD) is a triterpenoid saponin natural compound isolated from the Chinese herb Platycodon grandiflorum that has antiviral and antitumor properties. This study aimed to investigate the effects of DPD on glioblastoma (GBM) cells and to determine its intrinsic mechanism of action. Using a CCK8 assay, it was found that DPD significantly inhibited the growth of GBM cells. DPD-treated GBM cells contained swollen and degenerated mitochondria with empty vesicular bilayer membrane-like autophagic vesicle structures in the periphery of the mitochondria under transmission electron microscopy. DPD activated autophagy in GBM cells and induced a blockage of autophagic flux in the late stage. Transcriptomics identified differences in mitophagy-related genes, and analysis of the levels of the corresponding proteins indicated that mitophagy in GBM cells was induced mainly through BNIP3L. Increased expression of BNIP3L disrupts the Bcl-2-Beclin-1 complex, thereby releasing Beclin-1 and activating autophagy. Autophagy was inhibited after silencing of BNIP3L and overexpression of Bcl-2 in GBM cells, and the growth inhibitory effect of DPD was significantly reduced. This result demonstrated that DPD induces mitophagy in GBM cells through BNIP3L. Finally, activation of incomplete mitophagy in GBM cells by DPD through BNIP3L in vivo was demonstrated by establishing a mouse subcutaneous xenograft tumor model. In this study, in vitro and in vivo experiments established that DPD inhibited GBM cell growth by inducing BNIP3L-mediated incomplete mitophagy, which provides an experimental basis for studying new treatments of GBM. Graphical Abstract |
| format | Article |
| id | doaj-art-3fb78eeaa0924d08911642aa07f17a83 |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-3fb78eeaa0924d08911642aa07f17a832025-01-19T12:39:32ZengBMCCancer Cell International1475-28672025-01-0125111410.1186/s12935-025-03636-xDeapioplatycodin D inhibits glioblastoma cell proliferation by inducing BNIP3L-mediated incomplete mitophagyYu Sun0Guangze Zhu1Renshuang Zhao2Yaru Li3Hongyang Li4Yunyun Liu5Ningyi Jin6Xiao Li7Yiquan Li8Tiemei Liu9Department of Blood Transfusion, China-Japan, Union Hospital of Jilin UniversityAcademician Workstation of Jilin Province, Changchun University of Chinese MedicineMedical College, Yanbian UniversityMedical College, Yanbian UniversityDepartment of Blood Transfusion, China-Japan, Union Hospital of Jilin UniversityAcademician Workstation of Jilin Province, Changchun University of Chinese MedicineAcademician Workstation of Jilin Province, Changchun University of Chinese MedicineAcademician Workstation of Jilin Province, Changchun University of Chinese MedicineAcademician Workstation of Jilin Province, Changchun University of Chinese MedicineDepartment of Blood Transfusion, China-Japan, Union Hospital of Jilin UniversityAbstract Deapioplatycodin D (DPD) is a triterpenoid saponin natural compound isolated from the Chinese herb Platycodon grandiflorum that has antiviral and antitumor properties. This study aimed to investigate the effects of DPD on glioblastoma (GBM) cells and to determine its intrinsic mechanism of action. Using a CCK8 assay, it was found that DPD significantly inhibited the growth of GBM cells. DPD-treated GBM cells contained swollen and degenerated mitochondria with empty vesicular bilayer membrane-like autophagic vesicle structures in the periphery of the mitochondria under transmission electron microscopy. DPD activated autophagy in GBM cells and induced a blockage of autophagic flux in the late stage. Transcriptomics identified differences in mitophagy-related genes, and analysis of the levels of the corresponding proteins indicated that mitophagy in GBM cells was induced mainly through BNIP3L. Increased expression of BNIP3L disrupts the Bcl-2-Beclin-1 complex, thereby releasing Beclin-1 and activating autophagy. Autophagy was inhibited after silencing of BNIP3L and overexpression of Bcl-2 in GBM cells, and the growth inhibitory effect of DPD was significantly reduced. This result demonstrated that DPD induces mitophagy in GBM cells through BNIP3L. Finally, activation of incomplete mitophagy in GBM cells by DPD through BNIP3L in vivo was demonstrated by establishing a mouse subcutaneous xenograft tumor model. In this study, in vitro and in vivo experiments established that DPD inhibited GBM cell growth by inducing BNIP3L-mediated incomplete mitophagy, which provides an experimental basis for studying new treatments of GBM. Graphical Abstracthttps://doi.org/10.1186/s12935-025-03636-xDeapioplatycodin DBNIP3LMitophagyGlioblastoma |
| spellingShingle | Yu Sun Guangze Zhu Renshuang Zhao Yaru Li Hongyang Li Yunyun Liu Ningyi Jin Xiao Li Yiquan Li Tiemei Liu Deapioplatycodin D inhibits glioblastoma cell proliferation by inducing BNIP3L-mediated incomplete mitophagy Cancer Cell International Deapioplatycodin D BNIP3L Mitophagy Glioblastoma |
| title | Deapioplatycodin D inhibits glioblastoma cell proliferation by inducing BNIP3L-mediated incomplete mitophagy |
| title_full | Deapioplatycodin D inhibits glioblastoma cell proliferation by inducing BNIP3L-mediated incomplete mitophagy |
| title_fullStr | Deapioplatycodin D inhibits glioblastoma cell proliferation by inducing BNIP3L-mediated incomplete mitophagy |
| title_full_unstemmed | Deapioplatycodin D inhibits glioblastoma cell proliferation by inducing BNIP3L-mediated incomplete mitophagy |
| title_short | Deapioplatycodin D inhibits glioblastoma cell proliferation by inducing BNIP3L-mediated incomplete mitophagy |
| title_sort | deapioplatycodin d inhibits glioblastoma cell proliferation by inducing bnip3l mediated incomplete mitophagy |
| topic | Deapioplatycodin D BNIP3L Mitophagy Glioblastoma |
| url | https://doi.org/10.1186/s12935-025-03636-x |
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