PT  - JOURNAL ARTICLE
AU  - Xue Du
AU  - Ruoran Mi
AU  - Quanxin Qu
AU  - Ye Qu
AU  - Tianfu Yue
TI  - Effects of Geldanamycin on Expression of Bcl-2 in Human Cervical Cancer HeLa Cells
AID  - 10.1007/s11805-008-0113-4
DP  - 2008 Apr 01
TA  - Chinese Journal of Clinical Oncology
PG  - 113--117
VI  - 5
IP  - 2
4099  - http://www.cancerbiomed.org/content/5/2/113.short
4100  - http://www.cancerbiomed.org/content/5/2/113.full
SO  - Cancer Biol Med2008 Apr 01; 5
AB  - OBJECTIVE Geldanamycin, a natural product of Streptomyces geldanus, binds the heat shock protein 90 (Hsp90), a cell chaperone protein that interacts with Bcl-2. In this study, we investigated whether geldanamycin (GA) inhibits proliferation of HeLa cells through induction of apoptosis by decreasing the level of Bcl-2 expression.METHODS HeLa cells, a human cervical cell line, were cultured in vitro and treated with different concentrations of GA (0, 0.02, 0.2, 2, 10 μmol/L) for 24 h. or were treated for different lengths of time at a GA concentration of 10 μmol/L. Proliferation of the cells was analyzed by an MTT assay, and cell apoptosis was determined by staining the cells with annexin V. In addition, cellular mRNA levels for Bcl-2 and Hsp90 were determined by the semiquantitative polymerase chain reaction (PCR), and the levels of Bcl-2 and Hsp90 protein expression were determined by Western blots.RESULTS Treatment of cells with GA was found to inhibit HeLa cell proliferation in a concentration and time-dependent manner. The inhibition was a result of increased cellular apoptotic levels. Further analyses showed that while the mRNA and protein expression levels of Hsp90 were not affected, GA treatment significantly reduced the level of Bcl-2 mRNA and protein expression in a concentration-dependent manner that correlated with the observed inhibition of cell proliferation.CONCLUSION GA can inhibit proliferation and increase apoptosis of HeLa cells by decreasing the transcription and expression of an anti-apoptotic gene bcl-2, probably through interaction and functional inhibition of Hsp90.