THE SYNERGISTIC EFFECT OF GELDANAMYCIN AND TRICHOSTATIN A ON HUMAN BLADDER CELLS

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OBJECTIVE: Heat shock protein 90 (HSP90) is an ATPdependent molecular chaperone required for the stability and function of numerous oncogenic signaling proteins that determine the hallmarks of cancer. Therefore, HSP90 is known as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor. Inhibition of Hsp90 results in the induction of apoptosis in cancer cells, and may be accompanied by a reduction in chemotherapy resistance. This study is aimed to investigate, on transcriptional and protein levels, the synergic effects of unaccompanied and/or combined use of Geldanamycin (GA) and Trichostatin A (TSA) on the apoptotic pathway of human bladder cancer cell line T24. MATERIAL AND METHODS: The effect of geldanamisin (0–30 μM) on cell viability were determined by WST-1. The variation in the expression levels of CASP3 genes was transcriptionally determined by quantitative real-time PCR. The translational expressional levels of caspase-3, Bax and Bcl_2 genes were performed by western blot method. RESULTS: The use of GA alone and GA+TSA combination significantly down-regulated the antiapoptotic gene Bcl_2 while Caspase-3 and Bax expression were increased at translational levels. Cas3 mRNA level was also increased with respect to control (p 0.05). CONCLUSIONS: The use of geldanamycin+TSA combination reduced cell proliferation and induced apoptosis. Therefore, it can be suggested that HSP90 inhibitors may offer a new approach to consider in the treatment of bladder cancer.

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HSP90 inhibitor , Geldanamycin , Apoptosis , Bladder Cancer

Kocatepe Medical Journal

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Kocatepe Medical Journal