Abstract
ObjectivesCurdione is one of the active ingredients of a traditional Chinese herbal medicine-Curcuma zedoary and established anti-tumor effects. Uterine leiomyosarcoma (uLMS) is a rare gynecological malignancy, with no standard therapeutic regimen at present. The aim of this study was to explore the potential anti-tumor impact of curdione in uLMS and elucidate the underlying mechanisms.Methods In vitro functional assays were performed in the SK-UT-1 and SK-LMS-1 cell lines. The in vivo model of uLMS was established by subcutaneously injecting SK-UT-1 cells, and the tumor-bearing mice were intraperitoneally injected with curdione. Tumor weight and volume were measured at specific time points. The biosafety was evaluated by monitoring changes of body weight and the histopathology in the liver and kidney. The expression levels of relevant proteins were analyzed by western blotting and immunohistochemistry.ResultsCurdione decreased the viability and proliferation of uLMS cells in a concentration and time-dependent manner. In addition, the curdione-treated cells exhibited significantly higher rates of apoptosis and autophagic death. Curdione also decreased the tumor weight and volume in the SK-UT-1 xenograft model compared to the untreated control without affecting the body bodyweight or pathological injury of liver and kidney tissues. At the molecular level, the anti-tumor effects of curdione were mediated by indoleamine-2, 3-dioxygenase-1 (IDO1).ConclusionCurdione exhibited an anti-uLMS effect in vitro and in vivo; the underlying mechanism involved in IDO1 mediate apoptosis, autophagy, and G2/M phase arrest.
Highlights
Uterine leiomyosarcoma is a rare and aggressive gynecological malignancy, which is characterized by high recurrence rate, low mortality rate, distant metastases, and poor prognosis [1, 2]
The IDO1 inhibitor epacadostat was purchased from Selleck (S7910, Texas, USA) and autophagy inhibitor 3- Methyladenine was purchased from Selleck (S2767, Texas, USA), CCk8 was purchased from Dojindo (CK04, Kumamoto, Japan), Beyo ClickTM Edu-594 Cell Proliferation Kit was purchased from Beyotime (C0078S, Shanghai, China), and Annexin V-fluorescein isothiocyanate (FITC) cell apoptosis kit was purchased from Invitrogen (V13241, New York, California, USA)
Western blotting was performed to evaluate the effect of curdione on IDO1 expression, the results showed that, curdione significantly down-regulated IDO1 expression of Uterine leiomyosarcoma (uLMS) cells in a dose and time-dependent manner (Figures 6A, B)
Summary
Uterine leiomyosarcoma (uLMS) is a rare and aggressive gynecological malignancy, which is characterized by high recurrence rate, low mortality rate, distant metastases, and poor prognosis [1, 2]. It is the most common subtype of uterine sarcoma, and clinical manifestations are abnormal uterine bleeding, palpable pelvic mass, and lower abdominal pain. The therapeutic effects of curdione have been reported in breast cancer [19], while the potential anti-tumor effect in uLMS is still unclear
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