Bufalin induces growth inhibition, cell cycle arrest and apoptosis in human endometrial and ovarian cancer cells.

ABSTRACT

Bufalin is a traditional Chinese medicine and it induces apoptosis in certain human tumor cell lines. We investigated the effect of bufalin on three endometrial cancer cell lines, two ovarian cancer cell lines, and on normal human endometrial epithelial cells. Endometrial and ovarian cancer cells were treated with various concentrations of bufalin, and its effect on cell growth, cell cycle, apoptosis, and related measurements was investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that all endometrial and ovarian cancer cell lines were sensitive to the growth-inhibitory effect of bufalin, although normal endometrial epithelial cells were viable after treatment with the same doses of bufalin that induced growth inhibition in endometrial and ovarian cancer cells. Cell cycle analysis indicated that their exposure to bufalin decreased the proportion of cells in the S-phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by annexin V staining of externalized phosphatidylserine and loss of the transmembrane potential of mitochondria. This induction occurred in concert with the altered expression of genes related to cell cycle and apoptosis. These results suggest that bufalin may become a useful adjuvant therapy for endometrial and ovarian cancers with minimal side effects.