Abstract
BACKGROUND: Quercetin, a secondary metabolite derived from plants with both medicinal and edible values, has demonstrated potential in cancer treatment, including endometrial carcinoma. However, its anti-tumor effect on cancer stem-like cells (CSCs), a subpopulation considered to be a major driver of tumor recurrence and metastasis-remain largely unclear. AIM: This study aimed to evaluate the anti-tumor effects of Quercetin by targeting CSCs and suppressing their stemness properties. METHODS: CSCs were enriched using serum-free medium and treated with a range concentration of Quercetin. The STAT3/JAK2 signalling was detected by western blot after treatment with Quercetin. The effects of Quercetin on malignant behaviours in CSCs, including proliferation, cell cycle distribution, spheres formation and invasion, were further assessed. RESULTS: Quercetin treatment inhibited the formation and maintenance of spheres derived from endometrial carcinoma cell lines EMN8 and EMN21.It also downregulated the expression of stemness markers, including ALDH1A1, c-Myc, Nanog, and Oct4.We further revealed that estrogen receptor α (ERα) is critical for mediating the inhibitory effects of Quercetin on stemness and malignant behavior, suggesting that ERα sensitizes CSCs to Quercetin. Quercetin suppressed STAT3/JAK2 phosphorylation and subsequently inhibited the transcriptional activity of STAT3's downstream target gene, Oct4.These inhibitory effects were reversed by the STAT3 activator Colivelin. CONCLUSION: Our findings demonstrate that Quercetin targets the stemness of CSCs in an ERα-dependent manner, highlighting its potential as a promising therapeutic agent against CSCs to improve clinical outcomes in endometrial carcinoma.