Cited 0 times in Scipus Cited Count

Quercetin and chloroquine synergistically kill glioma cells by inducing organelle stress and disrupting Ca(2+) homeostasis

Jang, E | Kim, IY | Kim, H | Lee, DM | Seo, DY | Lee, JA | Choi, KS  | Kim, E
Biochemical pharmacology, 178. : 114098-114098, 2020
Journal Title
Biochemical pharmacology
Glioblastoma (GBM) remains one of the most uncompromising cancers, with a median survival of 15 months among those receiving maximal therapy. Therefore, new effective approaches are urgently required for the treatment of GBM. In this study, we show that combined treatments with the flavonoid quercetin and chloroquine (CQ), which is a lysosomotropic agent with antimalarial activity, synergistically induce caspase-independent cell death in malignant glioma cells. The combination of quercetin and CQ triggered excessive expansion of autolysosomes and lysosomes due to overloading with undigested cellular components and protein aggregates, leading to cell death, whereas quercetin alone increased autophagic flux. These results suggest that CQ-mediated lysosomal inhibition prolongs quercetin-mediated autophagic flux, resulting in autophagic catastrophe and severe endoplasmic reticulum (ER) stress. Additionally, we found that 1,4,5-triphosphate receptor (IP3R)-mediated Ca(2+) release from the ER and the following mitochondrial uniporter (MCU)-mediated Ca(2+) influx into mitochondria as well as ROS generation are critically involved in the cytotoxicity by this combination. Collectively, the lysosomal defects induced by quercetin plus CQ may trigger the stress to both the ER and mitochondria and consequently their functional defects, contributing to glioma cell death. The combination of quercetin and CQ may be an effective therapeutic option for GBM.


Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Ajou Authors
최, 경숙
Files in This Item:
There are no files associated with this item.


해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.