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

  • Kyoung-jin Min
  • Sk Abrar Shahriyar
  • Taeg Kyu KwonEmail author
Original Article


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.


Arylquin 1 Non-apoptotic cell death Lysosomal membrane permeabilization Prostate‐apoptosis‐response‐4 Cell death 



This work was supported by an NRF Grant funded by the Korea Government (MSIP) (2014R1A5A2010008 and NRF-2019R1A2C2005921) and a 2018 Scholar Research Grant from Keimyung University.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.


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Copyright information

© Korean Society of Toxicology 2019

Authors and Affiliations

  • Kyoung-jin Min
    • 1
  • Sk Abrar Shahriyar
    • 1
  • Taeg Kyu Kwon
    • 1
    Email author
  1. 1.Department of Immunology, School of MedicineKeimyung UniversityDaeguSouth Korea

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