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Deapioplatycodin D inhibits glioblastoma cell proliferation by inducing BNIP3L-mediated incomplete mitophagy

文献类型： 外文期刊

作者： Sun, Yu 1 ; Zhu, Guangze 3 ; Zhao, Renshuang 4 ; Li, Yaru 4 ; Li, Hongyang 1 ; Liu, Yunyun 3 ; Jin, Ningyi 3 ; Li, Xiao 3 ; Li, Yiquan 3 ; Liu, Tiemei 1 ;

作者机构： 1.Jilin Univ, Dept Blood Transfus, China Japan Union Hosp, Changchun 130033, Peoples R China

2.Jilin Cent Hosp, Dept Neurol, Jilin 132011, Peoples R China

3.Changchun Univ Chinese Med, Academician Workstat Jilin Prov, Changchun 130117, Peoples R China

4.Yanbian Univ, Med Coll, Yanji 133002, Peoples R China

5.Chinese Acad Agr Sci, Changchun Vet Res Inst, Changchun 130122, Peoples R China

6.Jingyue Econ & Technol Dev Zone,1035 Boshuo Rd, Changchun, Jilin, Peoples R China

关键词： Deapioplatycodin D; BNIP3L; Mitophagy; Glioblastoma

期刊名称：CANCER CELL INTERNATIONAL （ 影响因子：6.0； 五年影响因子：5.3 ）

ISSN：

年卷期： 2025 年 25 卷 1 期

页码：

收录情况： SCI

摘要： 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.

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