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

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Author(s)
Kyoung‑jin MinSk Abrar ShahriyarTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
한국독성학회지
Issued Date
2020
Volume
36
Issue
2
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
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine (의과대학)
Citation
Kyoung‑jin Min et al. (2020). Arylquin 1, a potent Par‑4 secretagogue, induces lysosomal membrane permeabilization‑mediated non‑apoptotic cell death in cancer cells. 한국독성학회지, 36(2), 167–173. doi: 10.1007/s43188-019-00025-1
Type
Article
ISSN
2234-2753
Source
https://link.springer.com/article/10.1007%2Fs43188-019-00025-1
DOI
10.1007/s43188-019-00025-1
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/42707
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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