Isoliquiritigenin induces cell death programs and reduces ECM accumulation in uterine leiomyoma

Abstract

Abstract Background Uterine leiomyomas, also known as fibroids, are the comment and high prevalence in women of reproductive age. Isoliquiritigenin (ISL), a licorice flavonoid, exerts variant biological properties. In this study, the effect of ISL on anti-proliferation of uterine leiomyoma was investigated. Methods Cell viability was determined using the MTT assay. The protein expression was assayed using Western blot analysis. Cell apoptosis was assayed using Annexin V-FITC/PI and Hoechst 33342 staining. Results The results showed that treatment of uterine leiomyoma ELT3 cells and primary uterine smooth muscle UtSMC cells with ISL alone or ISL plus estradiol (E2) reduced cell proliferation. Cotreatment with E2 and ISL inhibit G2/M and S phase arrest in ELT3 and UtSMC cells, respectively. The higher sub-G1 phase arrest and fluorescence intensity of Hoechst 33342 nucleus stain were observed in cotreatmenet of ELT3 cells with E2 and ISL compared with UtSMC cells. Furthermore, cotreated ELT3 cells with E2 and ISL induced apoptosis and autophagy cell death programs. The E2-enhanced mice uterine myometrium growth was reduced by ISL presence, resulting in reduced the myometrium layer. Moreover, ISL reduced extracellular matrix proteins and matrix metalloproteinase (MMPs) expression, whereas increased tissue inhibitor of MMPs (TIMPs) expression. Conclusion Our findings indicated the inhibitory effects of ISL on the animal model and indicated that ISL reduced ECM-related protein expression and cell proliferation in the leiomyoma cell line. Taken together, our results suggested that ISL could be considered as a new option for the treatment of uterine leiomyoma.