Anti-neoplastic effect of β-hydroxyisovalerylshikonin on a human choriocarcinoma cell line.

β-hydroxyisovalerylshikonin (β-HIVS), a compound isolated from the traditional asian medicinal herb Lithospermum radix, is an ATP non-competitive inhibitor of protein-tyrosine kinases such as v-Src and EGFR, and has been shown to induce apoptosis in several human tumor cell lines. We investigated the effect of β-HIVS in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of β-HIVS, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. An MTT assay showed that BeWo cells were sensitive to the growth inhibitory effect of β-HIVS. Cell cycle analysis indicated that exposure to β-HIVS 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 by the loss of mitochondrial transmembrane potential. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that β-HIVS may serve as a therapeutic agent for the treatment of choriocarcinoma.