Antiproliferative effect of bitter melon (momordica charantia) seed and fruit extracts through the non-genomic oestrogen receptor signaling pathway on oestrogen-sensitive endometrium cancer cells

<strong>Background and Aims:</strong> Momordica charantia has garnered much attention as an alternative medicine due to its phytopharmaceutical content and anti-cancer properties. This study aimed to demonstrate the anti-cancer potential of M. charantia fruit extract (McFE) and seed extract (McSE) by investigating their effects on the migration and proliferation of human endometrial cancer (EC) cells as well as on the activation (phosphorylation) of non-genomic oestrogen receptor (ER) signaling pathway kinases and caspase-9 phosphorylation. <strong><span class="ql-cursor"></span>Methods:</strong> McFE and McSE samples were extracted with ethanol using the maceration method. The MTT (3-[4,5-dimethylthiazol-2-yl]−2,5 diphenyl tetrazolium bromide) test was used to evaluate EC cell (RL 95-2) viability, Western blot was used to analyse protein phosphorylation, and cell migration was evaluated using a wound-healing assay. <strong>Results:</strong> Cell proliferation was inhibited by McSE and McFE, with IC₅₀ values of 134,8 μg/mL and 165,9 μg/ mL, respectively. The phosphorylation of non-genomic ER signaling kinases, such as extracellular signalregulated kinases (ERK1/2) (8.59-fold), P38 mitogen-activated protein kinase (P38MAPK) (13.99-fold), and protein kinase B (AKT) (4.52-fold), increased in comparison to control cells after a short (15 min.) treatment with low concentrations (1 nM) of 17 β-oestradiol. The phosphorylation of caspase-9 (Thr125 2.59 fold, Ser196 3.48 fold) was additionally elevated by oestradiol treatment. The activation of ERK1/2, P38MAPK and AKT, and the phosphorylation of caspase-9 were significantly decreased by treatment with McSE and McFE. Additionally, the relative closure of the scratch in the cell migration assay was significantly reduced after treatment with McSE and McFE. <strong>Conclusion:</strong> M. charantia can induce cell death in EC cells by preventing the phosphorylation of caspase-9 and non-genomic kinases involved in the ER signaling pathway. These findings imply that M. charantia could be used as an alternative supportive treatment for EC.&nbsp;