Overview
- DeBoer, C. et al. (1970) J. Antibiot. (Tokyo) 23, 442.
- Ochel, H.J. et al. (2001) Cell Stress Chaperones 6, 105.
- Goetz, M.P. et al. (2003) Ann. Oncol. 14, 1169.
- Stebbins, C.E. et al. (1997) Cell 89, 239.
Alomone Labs Geldanamycin inhibits cell proliferation of HeLa and Jurkat cells.HeLa (blue) or Jurkat cells (pink) were treated with different concentrations of Geldanamycin (#G-500) for 4 days. The number of live cells was measured by XTT cell proliferation assay kit, normalized to the control (100%) and plotted against the drug concentration.
Geldanamycin is a potent antitumor antibiotic1 active against more than 50 tumor cell lines.2 Hsp90 is a molecular chaperone that regulates the folding, assembly and conformational maturation of proteins. It has a key role in cell response to environmental stress and in maintaining the malignant phenotype of tumor cells.3
Geldanamycin binds into the ATPase binding pocket in Hsp90,4,5 and induces the degradation of proteins required by this chaparone to induce conformational maturation. Hsp90 client proteins include transcription factors (mutated p53, HIF-1a, EF-2),6,7 tyrosine kinases (v-Src, Bcr-Abl, erbB2),8,9 serine-threonine kinases (Raf-1),10,11 and the nuclear receptor family (androgen, estrogen).12 Hsp90 client proteins play important roles in the regulation of the cell cycle, cell growth, apoptosis, and oncogenesis, geldanamycin inhibits the proliferation of cultured cancer cells and shows anticancer activity in experimental animals.
The antitumor effects involve different mechanisms such as destabilization of mutant p53 protein (breast and prostate cell lines)13 cell cycle arrest,13 inhibition of c-Jun expression,14 destabilization of Raf-1, destruction of EF-2 kinase, and inhibition of telomerase activity.15 Recently, synergistic effects of Geldanamycin with cytotoxic drugs16,17 increased tumor cell sensitivity to radiation.18,19
