Natural resveratrol analogs differentially target endometriotic cells into apoptosis pathways

Abstract

The specific characteristics of endometriotic cells are their ability to evade the apoptotic machinery and abnormal response to apoptotic stimuli. Natural-originated compounds may constitute a beneficial strategy in apoptosis modulation in endometriosis. We investigated and compared the potency of natural resveratrol analogs, including piceatannol, polydatin, and pterostilbene, in targeting cell death pathways, including apoptosis-related morphologic and biochemical processes, alongside the modulation of the critical genes expression. Upon resveratrol and pterostilbene treatment, a significant reduction of endometriotic cell viability and an increased apoptotic proportion of cells were noted. The lower antiproliferative potential was found for piceatannol and polydatin. Endometrial stromal T HESC cells were significantly more resistant than endometriotic epithelial 12Z cells to the cytotoxic activity of all analyzed compounds. They differentially affected endometriotic cell viability, cell cycle, anti- and proapoptotic genes regulation, caspases expression and enzymatic activity, and DNA fragmentation. Pterostilbene-mediated endometriotic cell apoptosis modulation was confirmed to be most effective but without evident caspase 3 upregulation. Our study provides valuable insight into the apoptogenic activity of resveratrol and its natural analogs in endometriotic cells. Data obtained revealed the highest therapeutic potential of pterostilbene by effectively targeting cell death determinants in endometriosis, strengthening its optimization in further extensive research.

Molecular Mechanism of Resveratrol and Its Therapeutic Potential on Female Infertility

“…Caution is also needed while choosing the preferable dose, as lower doses of resveratrol were reported as anti-apoptotic and higher as pro-apoptotic due to the effect on SIRT1 and p53 [87]. Differences were also observed regarding the cell type, with endometriotic cells being more prone to apoptosis at higher concentrations of resveratrol (>100 µM) than endometrial [197].…”

“…It also induced dosedependent DNA fragmentation and caspase-3 and caspase-7 activity. ESCs were observed to be more resistant to its effect at higher concentrations (100,200, 400 µM) compared with 12Z cells [197]. Another study by Zou et al explored the effect of resveratrol on ectopic ESCs, where they showed that resveratrol promoted oxidative stress and inhibited the proliferation and migration of ESCs due to ferroptosis [181], a non-apoptotic, irondependent cell death.…”

Recent Developments in Nanoparticle Formulations for Resveratrol Encapsulation as an Anticancer Agent

“…RSV is known for its anticancerous properties, mediating apoptosis, cell growth, metastasis, and angiogenesis, as illustrated in Figure 2 [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. Its mechanism involves reducing angiogenesis and increasing apoptosis through the inhibition of vascular endothelial growth factor (VEGF) expression by downregulating hypoxia-inducible factor 1 (HIF-1) [ 76 , 77 ].…”

Modulation of wheatgrass (Triticum aestivum Linn) toxicity against breast cancer cell lines by simulated microgravity

“…MCF-7 and MDA-231 (cancerous cell lines), along with MCF-10 and skin fibroblast HDFa (non-cancerous cell lines), were seeded at a density of 1x10 4 cells per well in 96-well Clear Flat Bottom Polystyrene TC-Treated plates using a 1 × 8 Stripwell™ format. The cells were cultured in their respective media to a final volume of 100 µL/well ( Gołąbek-Grenda et al, 2023 ). The cancerous cell lines were cultured in Dulbecco's Modified Eagle Medium (DMEM), supplemented with fetal bovine serum (FBS) or bovine calf serum (BCS), antibiotics (penicillin–streptomycin), and glutamine.…”