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<p>The combination of the cytotoxic effect of progesterone at high micromolar concentrations on hormone-dependent tumor cells and the immunostimulatory effect of 5-androstenediol (5-AED) is of interest as a new strategy for antitumor therapy. 5-AED has no cytotoxic effect on hormone-dependent MCF-7 tumor cells at a concentration of 10 µM, while new 5-AED esters at micromolar concentrations inhibit their viability by 15 – 20% (<i>p</i> &lt; 0.05). Progesterone at a concentration of 10 µM inhibits MCF-7 cell viability by 27% (<i>p</i> &lt; 0.0001). The difference in the action of 5-AED and its derivatives can be explained by the fact that 5-AED esters are more lipophilic than 5-AED and therefore penetrate tumor cells better, according to a computer prediction using the SwissADME web application. The calculated octanol-water LogP values for 5-AED and progesterone are 3.4 and 3, respectively, while LogP ranges from 4.5 to 5.5 for 5-AED esters. Potential targets for the cytotoxic and immunotropic effects of the two classes of steroid hormones progestogens and androstenes were predicted using the PASS Online, SuperPred, and SwissTargetPrediction web applications. These included ADAM10, STAT3, NT-3, and NF-κB in addition to androgen and estrogen receptors. <i>In silico</i> analysis of potential toxicity and physicochemical characteristics revealed that all studied steroids were low-toxicity compounds and satisfied Lipinski’s rule of five. It was hypothesized that a pharmaceutical composition based on 5-AED and progesterone derivatives may exhibit cytotoxic and immunotropic effects.</p>

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On the Cytotoxic Effect of 5-Androstenediol, Its Derivatives, and Progesterone on Hormone-Dependent Tumor Cells

  • 期刊论文

  • 发表日期：

    2025年12月1日

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  • N. S. Vand,
  • G. A. Khodos,
  • D. Yu. Makarova,
  • V. P. Pakhomova,
  • O. V. Orlova,
  • E. I. Utepeshova,
  • M. E. Uspenskaya,
  • T. A. Fedotcheva

摘要

The combination of the cytotoxic effect of progesterone at high micromolar concentrations on hormone-dependent tumor cells and the immunostimulatory effect of 5-androstenediol (5-AED) is of interest as a new strategy for antitumor therapy. 5-AED has no cytotoxic effect on hormone-dependent MCF-7 tumor cells at a concentration of 10 µM, while new 5-AED esters at micromolar concentrations inhibit their viability by 15 – 20% (p < 0.05). Progesterone at a concentration of 10 µM inhibits MCF-7 cell viability by 27% (p < 0.0001). The difference in the action of 5-AED and its derivatives can be explained by the fact that 5-AED esters are more lipophilic than 5-AED and therefore penetrate tumor cells better, according to a computer prediction using the SwissADME web application. The calculated octanol-water LogP values for 5-AED and progesterone are 3.4 and 3, respectively, while LogP ranges from 4.5 to 5.5 for 5-AED esters. Potential targets for the cytotoxic and immunotropic effects of the two classes of steroid hormones progestogens and androstenes were predicted using the PASS Online, SuperPred, and SwissTargetPrediction web applications. These included ADAM10, STAT3, NT-3, and NF-κB in addition to androgen and estrogen receptors. In silico analysis of potential toxicity and physicochemical characteristics revealed that all studied steroids were low-toxicity compounds and satisfied Lipinski’s rule of five. It was hypothesized that a pharmaceutical composition based on 5-AED and progesterone derivatives may exhibit cytotoxic and immunotropic effects.