ReferenceID 2659
Platycodin D inhibits autophagy and increases glioblastoma cell death via LDLR upregulation
Mol Oncol
Targeting autophagy is a promising therapeutic approach in cancer therapy. Here, we screened 30 traditional herbal medicines to identify novel autophagy regulators and found that Platycodon grandiflorus (PG) and platycod
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Record Fields
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- Reference Id
- 2659
- Evidence Id
- 19249
- Core Evidence Id
- 19249
- Source Reference Id
- 5314
- Herb2 Reference Id
- HBREF006111
- Subject Paper Key
- HBIN040205_33931944
- Pubmed Id
- 33931944
- Doi
- 10.1002/1878-0261.12966
- Paper Title
- Platycodin D inhibits autophagy and increases glioblastoma cell death via LDLR upregulation
- Paper Abstract
- Targeting autophagy is a promising therapeutic approach in cancer therapy. Here, we screened 30 traditional herbal medicines to identify novel autophagy regulators and found that Platycodon grandiflorus (PG) and platycodin D (PD), a triterpenoid saponin from PG, inhibited autophagy in glioblastoma multiforme (GBM) cells. Mechanistically, PD prevented lysosomal degradation and the fusion between autophagosomes and lysosomes by inducing sequestration of free cholesterol in lysosomes. The autophagy inhibitory effect of PD was mimicked by both genetic and pharmacological inhibition of Niemann-Pick C1 (NPC1), which exports low-density lipoprotein (LDL)-derived cholesterol from lysosomes. Moreover, PD promoted the uptake of exogenous LDL cholesterol via upregulation of LDL receptor (LDLR), leading to further accumulation of cholesterol within lysosomes and GBM cell death. Importantly, these phenomena were more pronounced in LDLR-overexpressing GBM cells than in normal astrocytes. Finally, blockade of cholesterol uptake by LDLR knockdown reversed the PD-induced inhibition of autophagy and GBM cell growth. Our study proposes that PD could be a potent anti-GBM drug by disrupting cholesterol trafficking and autophagy.
- Journal
- Mol Oncol
- Publish Year
- 2021
- Experiment Subject
- overexpressing gbm cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Cancer; Glioblastoma Multiforme
- Paper Title Cn
- Paper Title En
- Platycodin D inhibits autophagy and increases glioblastoma cell death via LDLR upregulation
- Bilingual Status
- semi_complete