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- Title
- Kushenol E inhibits autophagy and impairs lysosomal positioning via VCP/p97 inhibition
- Author(s)
- Mincheol Kwon; Mina Jang; Gun-Hee Kim; Taehoon Oh; In Ja Ryoo; Hyung Won Ryu; Sei-Ryang Oh; Bo Yeon Kim; Jae-Hyuk Jang; Sung-Kyun Ko; Jong Seog Ahn
- Bibliographic Citation
- Biochemical Pharmacology, vol. 175, pp. 113861-113861
- Publication Year
- 2020
- Abstract
- Autophagy plays a major role in cell survival and has therefore been exploited as an important strategy in cancer therapy. In this study, we evaluated the autophagy-regulatory effects of kushenol E (KE), a bi-prenylated flavonoid isolated from Sophora flavescens and found that KE increased LC3B-II levels while inducing the formation of autophagic vacuoles and immature autophagosomes in HeLa and HCT116 cells. Transmission electron microscopy images revealed that KE treatment generates immature autophagosomes. Furthermore, KE inhibited autophagosome maturation as demonstrated by blocking the degradation of EGFP puncta in HeLa cells stably expressing EGFP-mRFP-LC3B. It also reduced lysosomal activity and cathepsin maturation by disrupting lysosomal positioning, subsequently inducing apoptosis. Further, a combinatorial approach employing cellular thermal shift assays, revealed valosin-containing protein (VCP)/p97 as a potential target protein of KE; the knockdown and overexpression of VCP/p97 confirmed its involvement in regulating lysosomal positioning for autophagy maturation via direct interactions with KE. Thus, KE may possess autophagy-regulating properties mediated by binding to VCP/p97.
- Keyword
- AnticancerAutophagyKushenol E (KE)Lysosomal positioningVCP/p97
- ISSN
- 0006-2952
- Publisher
- Elsevier
- DOI
- http://dx.doi.org/10.1016/j.bcp.2020.113861
- Type
- Article
- Appears in Collections:
- Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
Ochang Branch Institute > Natural Product Research Center > 1. Journal Articles
Ochang Branch Institute > 1. Journal Articles
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