title: Evaluation of the cytotoxic activity of diethylstilbestrol and its mono- and diphosphate towards prostatic carcinoma cells.
abstract: To evaluate a possible direct cytotoxic effect of diethylstilbestrol diphosphate (DESDP) in the treatment of prostate cancer we exposed three prostatic carcinoma cell lines (LNCaP, DU 145, and PC-3), 2 nonprostatic neoplastic cell lines (KB and EJ), and one nontransformed cell line (MRC-5) to diethylstilbestrol (DES), diethylstilbestrol monophosphate, and DESDP at levels occurring in patients' sera during p.o. DES therapy (2 to 5 ng/ml) or DESDP infusions (1 to 20 micrograms/ml), respectively. With 5 ng/ml of DES no effect was seen in LNCaP cells, even after 14 days of exposure. In contrast, drug levels attained during DESDP infusions showed marked, dose-dependent cytotoxicity towards all cell lines under study. Prostatic cells were not exceptionally sensitive. High-dose DES slightly stimulated the synthesis of prostatic acid phosphatase in LNCaP cells. Formation of foci of polygonal cells was induced by 5 micrograms/ml of DES in cultures of MRC-5 fibroblasts. We conclude that, at high doses, DES liberated from DESDP acts upon a regulatory or metabolic mechanism common to many if not all human cells. Preferential sensitivity of prostate cancer cells in vivo may be due to high local phosphatase activity and/or DES accumulation in prostatic tissue.
authors.affiliation: Institut für Physiologische Chemie der Universität München, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Schulz
authors.forename: H W
authors.initials: HW
authors.lastname: Bauer
authors.forename: W P
authors.initials: WP
authors.lastname: Brade
authors.forename: A
authors.initials: A
authors.lastname: Keller
authors.forename: F
authors.initials: F
authors.lastname: Fittler
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004054:Diethylstilbestrol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis; D011467:Prostate / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C048587:diethylstilbestrol monophosphate; D004054:Diethylstilbestrol; C004955:fosfestrol; D000135:Acid Phosphatase; D010744:Phosphoric Monoester Hydrolases