HSP90 inhibition potentiates oxidant-based antimelanoma action of novel thioquercetin derivatives by compromising AhR/CYP1A1 pathway - PubMed
2 days ago
- #Melanoma therapy
- #HSP90 inhibition
- #Thioquercetin derivatives
- Novel thioquercetin derivatives (thioQ, thioQ(OAc)4, thioQ(OAc)5) induce apoptotic cell death in melanoma cells at low micromolar concentrations, with selective toxicity compared to normal cells.
- Thioquercetins reduce spheroid-forming cells and suppress growth in 3D spheroid models, indicating efficacy in more complex tumor environments.
- Inhibition of HSP90 with 17-DMAG potentiates the antimelanoma action of thioquercetins by augmenting oxidative stress (increased superoxide, decreased antioxidant proteins SOD1 and PRDX1-2).
- Combined treatment impairs the AhR/CYP1A1 detoxification pathway by inhibiting AhR nuclear translocation and CYP1A1 expression, leading to enhanced cytotoxicity against melanoma cells.
- ThioQ(OAc)4 exhibits senolytic activity against cisplatin-induced senescent melanoma cells in selected experimental settings, suggesting potential for targeting senescent tumor cells.
- The study proposes further in vivo validation of thioquercetin derivatives combined with HSP90 inhibitors for designing more effective antimelanoma therapies.