Lewińska, AnnaWitkowski, WojciechSłaby, JuliaWnuk, MaciejStec, PaulinaPiotrowski, PiotrŻebrowski, MichałCybularczyk-Cecotka, MartynaDeręgowska, AnnaRomanchikova, NadezhdaZayakin, PawelLinē, AijaMoros, MaríaLitwinienko, GrzegorzLewińska, Anna2026-04-232026-04-232026-03-28Witkowski W, Słaby J, Wnuk M, Stec P, Piotrowski P, Żebrowski M, Cybularczyk-Cecotka M, Deręgowska A, Romanchikova N, Zayakin P, Linē A, Moros M, Litwinienko G, Lewińska A. HSP90 inhibition potentiates oxidant-based antimelanoma action of novel thioquercetin derivatives by compromising AhR/CYP1A1 pathway. Apoptosis. 2026 Mar 28;31(4):114. doi: 10.1007/s10495-026-02311-4.doi: 10.1007/s10495-026-02311-4https://rdb.ur.edu.pl/handle/item/95Dataset 1: Original data used to generate the results on the synthesis and characterization of QDs Dataset 2: Original data used to generate the results on the biological effects of QDsQuercetin, a plant-derived dietary flavonoid, has multifunctional biological activities, including anticancer action; however, its applications may be restricted due to limited bioavailability. Thus, novel synthetic quercetin derivatives (QDs) with improved properties and/or drug combinations should be designed and tested. In the present study, anticancer activity of fourteen newly synthesized QDs was investigated using four cellular models of melanoma, namely A375, MM370, G-361, and SH-4 cells. Thioquercetins (thioQ, thioQ(OAc)4, and thioQ(OAc)5), when used at low micromolar range, induced apoptotic cell death in melanoma cells compared to normal cells. Thioquercetins also reduced the population of spheroid-forming cells and suppressed the growth of A375 cells in 3D spheroid models. Thioquercetin-mediated antimelanoma action was potentiated upon heat shock protein 90 (HSP90) inhibition. Co-treatment with the HSP90 inhibitor 17-DMAG and thioquercetins augmented oxidative stress (increased superoxide production, decreased levels of antioxidant proteins SOD1, and PRDX1-2), and impaired the aryl hydrocarbon receptor (AhR)/cytochrome P450 1A1 (CYP1A1) signaling pathway-based detoxification of thioquercetins by the inhibition of AhR translocation to the nucleus and AhR-mediated stimulation of CYP1A1 expression leading to enhanced cytotoxic effects against melanoma cells. The senolytic activity of thioQ(OAc)4 with four acetylated hydroxy groups against cisplatin-induced senescent melanoma cells was also revealed in selected experimental settings. We suggest that the use of novel thioquercetin-based derivatives along with HSP90 inhibitors should be further validated in vivo and considered for the design of more effective antimelanoma strategies in the future.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Cytochrome P450HSP90 inhibitionMelanomaOxidative stressThioquercetinraw dataset