Captopril modulates hormone receptor concentration and inhibitsproliferation of human mammary ductal carcinoma cells in culture

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• 作者：Small Jr. ; William ; Molteni ; Agostino ; Kim ; Yoon T. ; Taylor ; Joann M. ; Chen ; Zehan ; Ward ; William F.
• 关键词：captopril ; hormone receptors ; lisinopril ; mammary carcinoma ; penicillamine
• 刊名：Breast Cancer Research and Treatment
• 出版年：1997
• 出版时间：1997
• 年：1997
• 卷：44
• 期：3
• 页码：217-224
• 全文大小：231 KB

文摘

The present study evaluated the effect of theangiotensin converting enzyme (ACE) inhibitor captopril on estrogen(ER) and progesterone (PR) receptor concentration and onproliferation in two lines of human mammary ductalcarcinoma cells in culture: T-47D (ER+/PR+) and Hs578T(ER&minus;/PR&minus;). The incorporation of [$^3$H]thymidine, validated by cellcount, served as an index of proliferation. Comparedto control cells, T-47D cells incubated for 48hrs in 1, 2, or 5 mM captopril(but not in 0.5 mM) exhibited a reductionin ER from 130 ± 6 to 32± 32 fmol/mg cytosolic protein, and an increasein PR from 1780 ± 120 to 2740± 400 fmol/mg protein (p < 0.05). Westernanalysis confirmed these drug-induced changes in the concentrationof immunoreactive receptor proteins. Captopril also induced theappearance of low but detectable PR in theHs578T cells at concentrations as low as 50&micro;M. Captopril inhibited the incorporation of [$3$H]thymidine byboth cell types during a 48 hr incubation,although Hs578T cells were 2–3 times more resistantthan were T–47D cells. This cytostatic effect ofcaptopril was not due to cytotoxicity as indicatedby $^51$Cr release, and was not accompanied bysignificant changes in cell cycle distribution as determinedby flow cytometry. The incorporation of [$^3$H]uridine (RNAsynthesis) and [$^14$C]alanine (protein synthesis) also were inhibitedby captopril, suggesting a general antimetabolic effect ofthe drug in the ductal carcinoma cells. Theseare novel actions of a common antihypertensive agent.In contrast, the nonthiol ACE inhibitor lisinopril, andpenicillamine, a thiol compound with virtually no ACEinhibitory activity, had no effect on any ofthese endpoints.