The licorice dietary component isoliquiritigenin chemosensitizes human uterine sarcoma cells to doxorubicin and inhibits cell growth by inducing apoptosis and autophagy via inhibition of m-TOR signaling

Abstract

Uterine sarcoma is a rare gynecologic cancer. Doxorubicin (Dox) is widely used for treating several cancers, including uterine sarcoma. However, multidrug resistance is a major clinical problem and a critical cause of treatment failure. Strategies for increasing chemosensitivity and reducing the dose of chemotherapeutic agents should be established to prevent drug side effects, and the development of new chemotherapeutic agents is crucial. Isoliquiritigenin (ISL) is a natural flavonoid with a chalcone structure isolated from licorice root. ISL exhibits significant anticancer activities against many cancer types. In this study, we investigated the antitumor effects of ISL on the human uterine sarcoma cancer cell line MES-SA and the multidrug-resistant human uterine sarcoma cancer cell lines MES-SA/Dx5 and MES-SA/Dx5-R. Our results showed that treatment with ISL alone or in combination with Dox significantly inhibited the growth of cancer cells and increased the proportion of cells in the sub-G1 phase. Flow cytometry revealed that ISL induced apoptosis and necrosis. In addition, ISL enhanced the expression of autophagy-associated protein light chain 3 beta-II and apoptosis-associated protein cleaved poly(ADP-ribose) polymerase. ISL also inhibited protein expression of Bcl-2 and phosphorylated mechanistic target of rapamycin. Moreover, taken together, the results indicate that licorice dietary component ISL can inhibit human uterine sarcoma cancer cells by inducing apoptosis and autophagy and can increase the chemosensitivity of the multidrug-resistant human uterine sarcoma cancer cells MES-SA/Dx5 and MES-SA//Dx5-R to doxorubicin. Therefore, ISL-containing food might be beneficial for enhance cancer chemotherapy.