Antiproliferative and antiangiogenic effects of ammonium tetrathiomolybdate in a model of endometriosis

• Published in: Life sciences (1973) 2021-12, Vol.287, p.120099-120099, Article 120099
• Main Authors: Delsouc, María Belén, Conforti, Rocío Ayelem, Vitale, Daiana Luján, Alaniz, Laura, Pacheco, Pablo, Andujar, Sebastián, Vallcaneras, Sandra Silvina, Casais, Marilina
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Ammonium; Ammonium molybdate; Ammonium tetrathiomolybdate; Angiogenesis; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; Antiangiogenic agents; Antiangiogenics; Antioxidants; Antiproliferatives; Atomic absorption spectroscopy; Blood vessels; Cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - physiology; Chelation; Copper; Disease Models, Animal; Drinking water; Electrochemiluminescence; Endometriosis; Endometriosis - drug therapy; Endometriosis - pathology; Endothelial cells; Female; Fibroblast growth factor 2; Gene expression; Growth factors; Immunohistochemistry; Lesions; Lipid peroxidation; Lipids; Mice; Mice, Inbred C57BL; Molybdenum - pharmacology; Molybdenum - therapeutic use; Oxidative stress; Pathology; Peroxidation; Platelet-derived growth factor; Proliferating cell nuclear antigen; Sex hormones; Spectral analysis; Spectrometry; Spectrophotometry
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.120099

Copper (Cu) is involved in the endometriosis progression. Herein, an experimental endometriosis model was used to evaluate whether its chelation with ammonium tetrathiomolybdate (TM) affects the proliferation and angiogenesis in endometriotic-like lesions and the participation of oxidative stress in these processes. Female C57BL/6 mice were divided into three groups: sham-operated mice, endometriosis-induced mice, and TM-treated endometriosis-induced mice. Each animal in the third group received 0.3 mg of TM/day in their drinking water from the postoperative 15th day. The samples were collected after one month of induced pathology. In peritoneal fluids, Cu and estradiol levels were determined by electrothermal atomic absorption spectrometry and electrochemiluminescence, respectively. Endometriotic-like lesions were processed for the analysis of cell proliferation by PCNA immunohistochemistry, the expression of angiogenic markers by RT-qPCR, the presence of endothelial cells by immunofluorescent staining, and oxidative stress applying spectrophotometric methods. TM treatment decreased Cu and estradiol levels, which were increased by this pathology. In lesions, TM induced: (a) a decrease in tissue weight and volume, (b) a decrease in PCNA-positive cells, (c) antiangiogenic effects by decreasing the number of blood vessels, the mRNA expression of fibroblast growth factor 2 (Fgf2) and platelet-derived growth factor subunit B (Pdgfb), and the presence of endothelial cells, (d) a decrease in antioxidant activity and an increase in lipid peroxidation. TM is a highly effective antiproliferative and antiangiogenic agent, modulating oxidative imbalance in endometriosis. Its anti-endometriotic potential is an attractive feature of TM as a possible non-hormonal treatment. •Ammonium tetrathiomolybdate is an effective antiproliferative and antiangiogenic agent.•Copper chelation suppresses the growth of endometriotic-like lesions.•Ammonium tetrathiomolybdate reduces estradiol levels in a model of endometriosis.•Copper chelation modulates oxidative imbalance in experimental endometriosis.