ArticleThe Journal of biological chemistry2015
The quinone methide aurin is a heat shock response inducer that causes proteotoxic stress and Noxa-dependent apoptosis in malignant melanoma cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Therapeutic Effect of Rosolic Acid against Endothelial Dysfunction in Diabetic Wistar Rats.Current medicinal chemistry · 2026Article
- Inhibition of UV-Induced Stress Signaling and Inflammatory Responses in SKH-1 Mouse Skin by Topical Small-Molecule PD-L1 Blockade.JID innovations : skin science from molecules to population health · 2024Article
- Systemic deuteration of SCID mice using the water-isotopologue deuterium oxide (DMolecular carcinogenesis · 2023Article
- Mefloquine induces ER stress and apoptosis in BRAFi-resistant A375-BRAFMolecular carcinogenesis · 2022Article
- Vemurafenib Drives Epithelial-to-Mesenchymal Transition Gene Expression in BRAF Inhibitor‒Resistant BRAFThe Journal of investigative dermatology · 2022Article
- Three novel piperidones exhibit tumor-selective cytotoxicity on leukemia cells via protein degradation and stress-mediated mechanisms.Pharmacological reports : PR · 2022Article
- Deuterium Oxide (DCancers · 2021Article
- The Endogenous Tryptophan-derived Photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) is a Nanomolar Photosensitizer that Can be Harnessed for the Photodynamic Elimination of Skin Cancer Cells in Vitro and in Vivo.Photochemistry and photobiology · 2021Article
- The sunless tanning agent dihydroxyacetone induces stress response gene expression and signaling in cultured human keratinocytes and reconstructed epidermis.Redox biology · 2020Article
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- Induction of apoptosis via proteasome inhibition in leukemia/lymphoma cells by two potent piperidones.Cellular oncology (Dordrecht, Netherlands) · 2018Article
- Differential correlations between changes to glutathione redox state, protein ubiquitination, and stress-inducible HSPA chaperone expression after different types of oxidative stress.Cell stress & chaperones · 2018Article
- HDAC and Ku70 axis- an effective target for apoptosis induction by a new 2-cyano-3-oxo-1,9-dien glycyrrhetinic acid analogue.Cell death & disease · 2018Article
- Noxa/HSP27 complex delays degradation of ubiquitylated IkBα in airway epithelial cells to reduce pulmonary inflammation.Mucosal immunology · 2018Article
- The BPhotochemistry and photobiology · 2017Article
- The isopeptidase inhibitor 2cPE triggers proteotoxic stress and ATM activation in chronic lymphocytic leukemia cells.Oncotarget · 2016Article
- Cancer Microenvironment and Endoplasmic Reticulum Stress Response.Mediators of inflammation · 2015Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Pharmacological induction of proteotoxic stress is rapidly emerging as a promising strategy for cancer cell-directed chemotherapeutic intervention. Here, we describe the identification of a novel drug-like heat shock response inducer for the therapeutic induction of proteotoxic stress targeting malignant human melanoma cells. Screening a focused library of compounds containing redox-directed electrophilic pharmacophores employing the Stress & Toxicity PathwayFinder(TM) PCR Array technology as a discovery tool, a drug-like triphenylmethane-derivative (aurin; 4-[bis(p-hydroxyphenyl)methylene]-2,5-cyclohexadien-1-one) was identified as an experimental cell stress modulator that causes (i) heat shock factor transcriptional activation, (ii) up-regulation of heat shock response gene expression (HSPA6, HSPA1A, DNAJB4, HMOX1), (iii) early unfolded protein response signaling (phospho-PERK, phospho-eIF2α, CHOP (CCAAT/enhancer-binding protein homologous protein)), (iv) proteasome impairment with increased protein-ubiquitination, and (v) oxidative stress with glutathione depletion. Fluorescence polarization-based experiments revealed that aurin displays activity as a geldanamycin-competitive Hsp90α-antagonist, a finding further substantiated by molecular docking and ATPase inhibition analysis. Aurin exposure caused caspase-dependent cell death in a panel of human malignant melanoma cells (A375, G361, LOX-IMVI) but not in non-malignant human skin cells (Hs27 fibroblasts, HaCaT keratinocytes, primary melanocytes) undergoing the aurin-induced heat shock response without impairment of viability. Aurin-induced melanoma cell apoptosis depends on Noxa up-regulation as confirmed by siRNA rescue experiments demonstrating that siPMAIP1-based target down-regulation suppresses aurin-induced cell death. Taken together, our data suggest feasibility of apoptotic elimination of malignant melanoma cells using the quinone methide-derived heat shock response inducer aurin.
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