Inhibitory effect of curcumin in human endometriosis endometrial cells via downregulation of vascular endothelial growth factor

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Curcumin treatment decreased human endometriotic stromal cell growth and survival by downregulating vascular endothelial growth factor (VEGF) and altering cell cycle progression.

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This in vitro study investigated how curcumin affects human endometriotic stromal cells, using samples from 14 patients with endometriosis and assessing cell purity, proliferation (MTT and H&E), cell-cycle distribution (flow cytometry), VEGF protein expression (immunohistochemistry), and apoptosis (Annexin V-FITC). Curcumin treatment decreased growth of both ectopic and eutopic stromal cells, with a curcumin dose of 50 µmol/l associated with increased G1-phase and decreased S-phase cell percentages. The authors also found that curcumin reduced VEGF expression, linking reduced cell survival to downregulation of VEGF-related signaling. A limitation explicitly implied by the design is that the work is confined to cultured stromal cells rather than in vivo testing in this report. This paper is centrally about endometriosis — it tests curcumin’s inhibitory effects on human endometriotic and eutopic endometrial stromal cells via VEGF downregulation.

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Abstract

Endometriosis, which affects up to 10% of women of reproductive age, is defined as endometrial-like gland and stroma tissue growths outside the uterine cavity. Despite increasing research efforts, there are no current effective treatment methods for this disease, therefore investigations for therapeutic strategies are of primary concern. In preliminary work, the authors demonstrated that curcumin inhibits endometriosis in vivo. The present in vitro study aimed to investigate the association between endometriotic stromal cells and curcumin and to clarify the underlying mechanism of action. A total of 14 patients with endometriosis were enrolled in the present study. The purity of endometrial stromal cell cultures was proven by standard immunofluorescent staining of vimentin. The cell proliferation and curcumin effects on endometrial stromal cells were assessed by the MTT assay and Hematoxylin and Eosin staining. For cell cycle analysis, phase distribution was detected by flow cytometry. Vascular endothelial growth factor (VEGF) protein expression was examined using immunohistochemistry staining. Apoptosis was assessed using Annexin V‑fluorescein isothiocyanate staining. The results indicated that the treatment of curcumin decreased human ectopic and eutopic stromal cell growth. Following treatment with curcumin, human endometriotic stromal cells demonstrated an increased percentage of G1‑phase cells and decreased percentages of S‑phase cells, particularly in the group treated with 50 µmol/l curcumin. Treatment with curcumin additionally decreased expression of VEGF. The data provide evidence that curcumin reduces cell survival in human endometriotic stromal cells, and this may be mediated via downregulation of the VEGF signaling pathway.
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Print ISSN: 1791-2997 Online ISSN: 1791-3004 International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease. International Journal of Oncology is an international journal devoted to oncology research and cancer treatment. Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery. Oncology Reports is an international journal devoted to fundamental and applied research in Oncology. Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine. Oncology Letters is an international journal devoted to Experimental and Clinical Oncology. Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology. International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis. Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology. Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition. Publishes open-access research on using epigenetics to advance understanding and treatment of human disease. An International Open Access Journal Devoted to General Medicine. Article - Authors: - Pages: 5611-5617|Published online on: August 14, 2017https://doi.org/10.3892/mmr.2017.7250 - Expand metrics + Endometriosis, which affects up to 10% of women of reproductive age, is defined as endometrial-like gland and stroma tissue growths outside the uterine cavity. Despite increasing research efforts, there are no current effective treatment methods for this disease, therefore investigations for therapeutic strategies are of primary concern. In preliminary work, the authors demonstrated that curcumin inhibits endometriosis in vivo. The present in vitro study aimed to investigate the association between endometriotic stromal cells and curcumin and to clarify the underlying mechanism of action. A total of 14 patients with endometriosis were enrolled in the present study. The purity of endometrial stromal cell cultures was proven by standard immunofluorescent staining of vimentin. The cell proliferation and curcumin effects on endometrial stromal cells were assessed by the MTT assay and Hematoxylin and Eosin staining. For cell cycle analysis, phase distribution was detected by flow cytometry. Vascular endothelial growth factor (VEGF) protein expression was examined using immunohistochemistry staining. Apoptosis was assessed using Annexin V‑fluorescein isothiocyanate staining. The results indicated that the treatment of curcumin decreased human ectopic and eutopic stromal cell growth. Following treatment with curcumin, human endometriotic stromal cells demonstrated an increased percentage of G1‑phase cells and decreased percentages of S‑phase cells, particularly in the group treated with 50 µmol/l curcumin. Treatment with curcumin additionally decreased expression of VEGF. The data provide evidence that curcumin reduces cell survival in human endometriotic stromal cells, and this may be mediated via downregulation of the VEGF signaling pathway. Copy and paste a formatted citation Spandidos Publications style Cao H, Wei YX, Zhou Q, Zhang Y, Guo XP and Zhang J: Inhibitory effect of curcumin in human endometriosis endometrial cells via downregulation of vascular endothelial growth factor. Mol Med Rep 16: 5611-5617, 2017. APA Cao, H., Wei, Y., Zhou, Q., Zhang, Y., Guo, X., & Zhang, J. (2017). Inhibitory effect of curcumin in human endometriosis endometrial cells via downregulation of vascular endothelial growth factor. Molecular Medicine Reports, 16, 5611-5617. https://doi.org/10.3892/mmr.2017.7250 MLA Cao, H., Wei, Y., Zhou, Q., Zhang, Y., Guo, X., Zhang, J."Inhibitory effect of curcumin in human endometriosis endometrial cells via downregulation of vascular endothelial growth factor". Molecular Medicine Reports 16.4 (2017): 5611-5617. Chicago Cao, H., Wei, Y., Zhou, Q., Zhang, Y., Guo, X., Zhang, J."Inhibitory effect of curcumin in human endometriosis endometrial cells via downregulation of vascular endothelial growth factor". Molecular Medicine Reports 16, no. 4 (2017): 5611-5617. https://doi.org/10.3892/mmr.2017.7250

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Condition tags

endometriosis

MeSH descriptors

Curcumin Endometriosis Signal Transduction Vascular Endothelial Growth Factors Adult Apoptosis Biomarkers Cell Proliferation Cell Proliferation Curcumin Curcumin Endometriosis Endometriosis Female Flow Cytometry Humans Immunohistochemistry Middle Aged Signal Transduction Stromal Cells

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