Induction of apoptosis by estramustine phosphate mediated by phosphorylation of bcl-2

Estramustine phosphate (EMP) is an anti-microtubule agent that induces apop tosis of glioma cells. We investigated whether EMP caused apoptosis through the alkylating effect of its nitrogen mustard component or by phosphorylat ion of bcl-2 like other anti-microtubule agents in normal human astrocyte a nd human malignant glioma cell lines. Apoptosis was seen in glioma cells tr eated either with nitrogen mustard or EMP and expression of bcl-2 mRNA was not changed by exposure to the drug. An immunoprecipitation study only foun d phosphorylation bcl-2 in glioma cells exposed to EMP and not in cells exp osed to nitrogen mustard. These results indicate that induction of apoptosi s in glioma cells by EMP is mediated by phosphorylation of bcl-2.