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

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Abstract

The present study evaluated the effect of the angiotensin converting enzyme (ACE) inhibitor captopril on estrogen (ER) and progesterone (PR) receptor concentration and on proliferation in two lines of human mammary ductal carcinoma cells in culture: T-47D (ER+/PR+) and Hs578T (ER−/PR−). The incorporation of [3H]thymidine, validated by cell count, served as an index of proliferation. Compared to control cells, T-47D cells incubated for 48 hrs in 1, 2, or 5 mM captopril (but not in 0.5 mM) exhibited a reduction in ER from 130 ± 6 to 32 ± 32 fmol/mg cytosolic protein, and an increase in PR from 1780 ± 120 to 2740 ± 400 fmol/mg protein (p < 0.05). Western analysis confirmed these drug-induced changes in the concentration of immunoreactive receptor proteins. Captopril also induced the appearance of low but detectable PR in the Hs578T cells at concentrations as low as 50 µM. Captopril inhibited the incorporation of [3H]thymidine by both cell types during a 48 hr incubation, although Hs578T cells were 2–3 times more resistant than were T–47D cells. This cytostatic effect of captopril was not due to cytotoxicity as indicated by 51Cr release, and was not accompanied by significant changes in cell cycle distribution as determined by flow cytometry. The incorporation of [3H]uridine (RNA synthesis) and [14C]alanine (protein synthesis) also were inhibited by captopril, suggesting a general antimetabolic effect of the drug in the ductal carcinoma cells. These are novel actions of a common antihypertensive agent. In contrast, the nonthiol ACE inhibitor lisinopril, and penicillamine, a thiol compound with virtually no ACE inhibitory activity, had no effect on any of these endpoints.

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Authors and Affiliations

  1. Department of Radiology, Northwestern University Medical School, Chicago, Illinois, USA

    William Small Jr., Yoon T. Kim, Joann M. Taylor & William F. Ward

  2. Department of Pathology, Northwestern University Medical School, Chicago, Illinois, USA

    Agostino Molteni

  3. Resurrection Medical Center, Chicago, Illinois, USA

    Yoon T. Kim

  4. The Lurie Cancer Center, Northwestern University Medical School, Chicago, Illinois, USA

    Zehan Chen

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  1. William Small Jr.
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  2. Agostino Molteni
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  3. Yoon T. Kim
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  4. Joann M. Taylor
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  5. Zehan Chen
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  6. William F. Ward
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Small, W., Molteni, A., Kim, Y.T. et al. Captopril modulates hormone receptor concentration and inhibits proliferation of human mammary ductal carcinoma cells in culture. Breast Cancer Res Treat 44, 217–224 (1997). https://doi.org/10.1023/A:1005827119296

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