Esculetin inhibits endometrial cancer proliferation and promotes apoptosis via hnRNPA1 to downregulate BCLXL and XIAP.

Endometrial cancer represents one of the most common gynecological tumors in the world. Advanced and relapsed patients rely on drug therapy. Therefore, it is extremely important to seek more effective targeted drugs. This study found that esculetin has an anti-tumor effect on endometrial cancer through cellular proliferation and apoptosis. At the same time, its anti-tumor effect has also been verified in human endometrial cancer xenograft models in nude mice. Western blot results showed that BCLXL, XIAP, and pAKT protein expression level were down-regulated. A pulldown experiment and LC-MS/MS analysis technology revealed that esculetin targets the hnRNPA1 protein. Cellular proliferation experiments following si-hnRNPA1 transfection verified the tumor-promoting effect of hnRNPA1 in endometrial cancer cells. Nuclear and cytoplasmic separation experiment demonstrated esculetin affecting the export of the hnRNPA1/mRNA complex from the nucleus into the cytoplasm. Thus, esculetin targets hnRNPA1, thereby downregulates BCLXL and XIAP mRNA transcription and translation, resulting in apoptosis and an arrest in proliferation.