Fig 3. The hypersensitivity of Rc cells to Hsp90 inhibitors can be counteracted by reducing activated pathways and metabolic resources.

(A) Scheme of the treatment and analysis regimen. (B) Concentration-dependent induction of cell death of N and Rc cells by GA, PU, and PX after 48 hrs of treatment. (C-E) Impact on GA-induced cell death of Rc pretreated with AZ628 and PD98059 (both 20 μM, 4 hrs) (panel C) or pre-cultured in low glucose (1 g/l) (panel D) or in hypoxia (1% O₂) for 24 hrs (panel E); low glucose and hypoxic conditions were maintained during the 48 hrs treatment with GA. Note that the data for GA-treated N and Rc cells (solid black and red lines) are identical to those of panel B and reproduced here for better visualization. Averages with standard deviation of 3 experiments are shown. (F) Immunoblots of the indicated Hsp90 clients from cells treated with GA for 24 hrs at the indicated concentrations; the filter stained with Ponceau S serves as loading control.