Limonin attenuates the stemness of cervical carcinoma cells by promoting YAP nuclear-cytoplasmic translocation

Abstract

This work aimed to investigate the role and related mechanism of limonin in regulating the stemness of cervical carcinoma (CC) cells. In the present study, we constructed adriamycin-resistant CC cells and found that they exhibited greater stemness than parental cells. Additionally, limonin attenuated the stemness of CC cells that were resistant or sensitive to adriamycin, as evidenced by the decreases in spheroid formation capacity, stemness markers expression and ALDH1 activity, whereas limonin did not affect the viability of normal cervical epithelial cells. Furthermore, limonin enhanced adriamycin sensitivity and attenuated adriamycin resistance in CC cells. Mechanistically, the nuclear-cytoplasmic translocation of YAP, not TAZ, was promoted by limonin in CC cells. Additionally, YAP overexpression attenuated the inhibitory effects of limonin on CC cell stemness. Therefore, limonin can attenuate the stemness, and thus the chemoresistance, of CC cells by promoting the nuclear-cytoplasmic translocation of YAP.

Keywords: Cervical carcinoma; Limonin; Nuclear-cytoplasmic translocation; Stemness; YAP.