Academic Journal
Platycodin D inhibits autophagy and increases glioblastoma cell death via LDLR upregulation
| العنوان: | Platycodin D inhibits autophagy and increases glioblastoma cell death via LDLR upregulation |
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| المؤلفون: | Sol Ji Lee, Yu‐Jeong Choi, Hyo In Kim, Hyo Eun Moon, Sun Ha Paek, Tai Young Kim, Seong‐Gyu Ko |
| المصدر: | Molecular Oncology, Vol 16, Iss 1, Pp 250-268 (2022) |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | autophagy, cholesterol, GBM, LDLR, lysosome, platycodin D, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1878-0261 1574-7891 53438825 |
| Relation: | https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261 |
| DOI: | 10.1002/1878-0261.12966 |
| URL الوصول: | https://doaj.org/article/43ba14e16d454de18473b5343882518d |
| رقم الانضمام: | edsdoj.43ba14e16d454de18473b5343882518d |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 18780261 15747891 53438825 |
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| DOI: | 10.1002/1878-0261.12966 |