계명대학교 의학도서관 Repository

Arylquin 1, a potent Par‑4 secretagogue, induces lysosomal membrane permeabilization‑mediated non‑apoptotic cell death in cancer cells

Metadata Downloads
Author(s)
Kyoung‑jin MinSk Abrar ShahriyarTaeg Kyu Kwon
Publication Year
2020
Keyword
Arylquin 1Non-apoptotic cell deathLysosomal membrane permeabilizationProstate‐apoptosis‐response‐4Cell death
Abstract
Arylquin 1, a small-molecule prostate-apoptosis-response-4 (Par-4) secretagogue, targets vimentin to induce Par-4 secretion. Secreted Par-4 binds to its receptor, 78-kDa glucose-regulated protein (GRP78), on the cancer cell surface and induces apoptosis. In the present study, we investigated the molecular mechanisms of arylquin 1 in cancer cell death. Arylquin 1 induces morphological changes (cell body shrinkage and cell detachment) and decreases cell viability in various cancer cells. Arylquin 1-induced cell death is not inhibited by apoptosis inhibitors (z-VAD-fmk, a pan-caspase inhibitor), necroptosis inhibitors (necrostatin-1), and paraptosis inhibitors. Furthermore, arylquin 1 significantly induces reactive oxygen species levels, but antioxidants [N-acetyl-l-cysteine and glutathione ethyl ester] do not inhibit arylquin 1-induced cell death. Furthermore, Par-4 knock-down by small interfering RNA confers no effect on cytotoxicity in arylquin 1-treated cells. Interestingly, arylquin 1 induces lysosomal membrane permeabilization (LMP), and cathepsin inhibitors and overexpression of 70-kDa heat shock protein (HSP70) markedly prevent arylquin 1-induced cell death. Therefore, our results suggest that arylquin 1 induces non-apoptotic cell death in cancer cells through the induction of LMP.
Alternative Title
Arylquin 1, a potent Par‑4 secretagogue, induces lysosomal membrane permeabilization‑mediated non‑apoptotic cell death in cancer cells
Department
Dept. of Immunology (면역학)
Publisher
School of Medicine (의과대학)
Citation
한국독성학회지, Vol.36(2) : 167-173, 2020
Type
Article
ISSN
2234-2753
DOI
10.1007/s43188-019-00025-1
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/42707
Authorize & License
  • AuthorizeOpen
Files in This Item:

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