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• W4387396331 abstract "Uterine leiomyomas are benign tumors composed of an abundance of disorganized extracellular matrix (ECM). We have demonstrated that the expression of ECM proteins including collagen-1A1 and glycosylated proteoglycans are modulated by curcumin. Curcumin and its two derivatives, demethoxy curcumin (DMC) and bis-demethoxy curcumin (BDMC) form the curcuminoids in the spice turmeric. Furthermore, integrative medicine approach for care of uterine leiomyomas is on the rise as patients understand the role of biologically based interventions and therapeutics. As such, our first objective was to understand the modulating role of curcuminoids on the matrix proteins. Vitamin D is another nutritional supplement with potential value for treating leiomyomas. Its efficacy in ECM remodeling, as shown by in-vitro studies, led to our second objective, to study the effect on production of ECM proteins in response to a combination of curcumin and Vitamin D. Leiomyoma (L) and myometrial (M) cell lines were cultured in the laboratory. Purified curcuminoids were obtained from Sabinsa Corporation NJ. Curcumin and Vitamin D were commercially obtained. Proteomic analysis included western blot analysis and immunohistochemistry. Leiomyoma cells, in response to treatment with all three curcuminoids individually or in combination, demonstrated a significant, concentration dependent decrease of extracellular matrix proteins including collagen-1A1 and fibronectin. Compared to the untreated leiomyoma control, at the concentration of 20μM, in response to the 24hr treatment with curcuminoids, the fold decrease in collagen-1A1 ranged from 2.5-fold to 4.14-fold (p<0.05). Comparatively, only DMC induced collagen-1A1 decrease (1.56+/-0.34-fold) in the normal myometrial cells. Similarly, fibronectin protein decrease ranged from 1.33-fold to 1.76-fold. Pathways involved in matrix development and modulation, demonstrated differential expression in response to curcuminoids. Activation of the AKT was significantly decreased on treatment with all compounds in leiomyoma cells (1.42-2.21-fold) but not in the myometrial cells. Significant decrease in NFkB was observed in both the cell lines (L and M) in response to curcumin as compared to other curcuminoids. Interestingly, curcuminoids at lower concentrations increased the Vitamin D receptor protein expression (1.56+/-0.27) in leiomyoma cells. Even though Vitamin D induced decrease in collagen-1A1 protein in leiomyoma cells, combination of curcumin and Vitamin D did not result in a synergistic response. Human uterine leiomyoma cells demonstrate a decrease in ECM production in response to the three curcuminoids individually as well as in combination. Differential effect on pathways involved in ECM modulation, in myometrial and leiomyoma cells may explain the protective effect of curcumin on normal cells and/or detrimental effect on tumor cells" @default.
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• W4387396331 date "2023-10-01" @default.
• W4387396331 modified "2023-10-07" @default.
• W4387396331 title "CURCUMIN, CURCUMINOIDS, VITAMIN D AND PRODUCTION OF EXTRACELLULAR MATRIX PROTEINS IN UTERINE FIBROIDS" @default.
• W4387396331 doi "https://doi.org/10.1016/j.fertnstert.2023.08.611" @default.
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