BACKGROUND: Geldanamycin (GA) can be considered a relatively new component with 
a promising mode of action against human malignancies. It specifically targets 
heat shock protein 90 (Hsp90) and interferes with its function as a molecular 
chaperone.
METHODS: In this study, we have investigated the effects of geldanamycin on the 
regulation of Hsp90-dependent oncogenic signaling pathways directly implicated 
in cell cycle progression, survival and motility of human urinary bladder cancer 
cells. In order to assess the biological outcome of Hsp90 inhibition on RT4 
(grade I) and T24 (grade III) human urinary bladder cancer cell lines, we 
applied MTT assay, FACS analysis, Western blotting, semi-quantitative (sq) 
RT-PCR, electrophoretic mobility shift assay (EMSA), immunofluorescence and 
scratch-wound assay.
RESULTS: We have herein demonstrated that, upon geldanamycin treatment, bladder 
cancer cells are prominently arrested in the G1 phase of cell cycle and 
eventually undergo programmed cell death via combined activation of apoptosis 
and autophagy. Furthermore, geldanamycin administration proved to induce 
prominent downregulation of several Hsp90 protein clients and downstream 
effectors, such as membrane receptors (IGF-IR and c-Met), protein kinases (Akt, 
IKKα, IKKβ and Erk1/2) and transcription factors (FOXOs and NF-κΒ), therefore 
resulting in the impairment of proliferative -oncogenic- signaling and reduction 
of cell motility.
CONCLUSIONS: In toto, we have evinced the dose-dependent and cell line-specific 
actions of geldanamycin on cell cycle progression, survival and motility of 
human bladder cancer cells, due to downregulation of critical Hsp90 clients and 
subsequent disruption of signaling -oncogenic- integrity.