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인지 및 사회성 연구단
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Platycodin D inhibits autophagy and increases glioblastoma cell death via LDLR upregulation

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Title
Platycodin D inhibits autophagy and increases glioblastoma cell death via LDLR upregulation
Author(s)
Sol Ji Lee; Choi, Yu-Jeong; Kim, Hyo In; Moon, Hyo Eun; Paek, Sun Ha; Tai Young Kim; Ko, Seong-Gyu
Publication Date
2022-01
Journal
Molecular Oncology, v.16, no.1, pp.250 - 268
Publisher
John Wiley and Sons Ltd
Abstract
© 2021 The Authors. Published by Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.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.
URI
https://pr.ibs.re.kr/handle/8788114/11219
DOI
10.1002/1878-0261.12966
ISSN
1574-7891
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > 1. Journal Papers (저널논문)
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