Infusion of high doses of diethylstilbestrol-diphosphate (DESDP) administered to patients relapsing on conventional androgen-suppressing therapy of carcinoma of the prostate often leads to significant improvement of the patient’s quality of life. The benefits of DESDP have been ascribed to its specific cytotoxic activity towards prostatic carcinoma cells. To evaluate the tissue specificity of the cytotoxic effect, we exposed three prostatic carcinoma cell lines (LNCaP, DU 145, and PC-3), three non-prostatic neoplastic cell lines (KB: epidermoid carcinoma, EJ: Bladder carcinoma, Daudi: Burkitt lymphoma), and one non-transformed embryonic fibroblast line (MRC-5) to diethylstilbestrol (DES), DES monophosphate, and DESDP, at levels comparable to those occurring in patients’ sera during DESDP infusions. At concentrations of 1–20 µg/ml the drugs showed marked, dose-dependent cytotoxicity towards all cell lines under study. The variation of the magnitude of the response among the different cell lines was considerable. In LNCaP cells the synthesis of prostatic acid phosphatase was monitored. We found that DES slightly stimulates prostatic acid phosphatase production. Formation of focuses of polygonal cells in MRC-5 cultures was induced by 7.5 µg/ml DES monophosphate. We conclude that at high doses DES liberated from DESDP acts upon a general biochemical or regulatory pathway. Preferential sensitivity of prostate cancer cells in vivo may be due to high local phosphatase activity and/or DES accumulation in prostatic tissue.

Keywords:
Diethylstilbestrol-diphosphate, Cytotoxicity, Prostatic carcinoma, Cell lines
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© 1988 S. Karger AG, Basel
1988
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