Toward Non-Hormonal Treatment of Endometriosis: Selective Antiproliferative and Pro-Apoptotic Effects of a Boron–Curcumin–Piperine Combination on Eutopic Endometrial Cells from Women with Endometriosis

In: Pharmaceuticals · 2026 · vol. 19(11) , pp. 1767 · doi:10.3390/ph19111767 · W7225637116
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A non-hormonal combination of sodium pentaborate, curcumin, and piperine selectively reduced viability and induced apoptosis in eutopic endometrial cells from women with endometriosis compared to controls.

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Abstract

Background/Objectives: Current medical treatments for endometriosis are largely hormonal and are limited by side effects and recurrence. We investigated whether a combination of sodium pentaborate pentahydrate, curcumin, and piperine selectively inhibits eutopic endometrial cells from women with endometriosis. Methods: Stromal- and glandular-enriched primary cultures were established from endometrial biopsies of four women with surgically and histologically confirmed endometriosis and four women without endometriosis. Cells were treated with the combination (50–500 μg/mL) for 24–72 h. Viability was measured by MTS assay, and half-maximal inhibitory concentrations (IC50) were estimated for each donor. Apoptosis was assessed by annexin V/propidium iodide flow cytometry at each donor’s approximate IC50. Results: Viability decreased in a dose- and time-dependent manner. At 48 h, IC50 values were approximately two-fold higher in control-derived than in endometriosis-derived cells for both glandular (321.3 ± 89.6 vs. 160.4 ± 40.1 μg/mL) and stromal (351.8 ± 59.4 vs. 179.0 ± 29.9 μg/mL) cells (selectivity indices 2.00 and 1.97), with complete separation between groups (Cohen’s d 2.3 and 3.7; Mann–Whitney p = 0.029, the minimum attainable with four donors per group). The combination increased apoptosis compared with untreated cells from the same donor in both glandular (54.5 ± 17.2% vs. 8.7 ± 4.9%; p = 0.022) and stromal (55.2 ± 8.0% vs. 8.4 ± 6.5%; p < 0.001) cells, with no difference between cell types (p = 0.95). Conclusions: This non-hormonal combination selectively reduced the viability of eutopic endometrial cells from women with endometriosis and induced apoptosis in these cells in vitro, with comparable potency in the enriched stromal and glandular fractions. These preliminary findings warrant validation in lesion-derived cells and in vivo models.

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