Myrothecine A modulates the proliferation of HCC cells and the maturation of dendritic cells through downregulating miR-221.

Abstract

Myrothecine A, characterized from the extracts of myrothecium roridum strain IFB-E012, isolated as endophytic fungi found in the traditional Chinese medicinal plant Artemisia annua. Here we investigated its roles on anti-tumor and immune regulation in vitro. Dendritic cells (DCs) are the most potent antigen presenting cells in immune responses. Recent studies have indicated that miRNAs are indispensable in regulating the development, differentiation, maturation and function of DC. MiR-221, acted as an oncogene, is an important regulator in cancer development by binding to 3 untranslated regions (3 UTR) of target mRNA. Here, we investigated whether myrothecine A could inhibit cell proliferation in hepatocellular carcinoma (HCC) cell line SMMC-7721 by regulating miR-221. The HCC cells were treated with myrothecine A at different concentration, and the cell growth ability was measured by MTT assay. Then we observed whether myrothecine A could affect the maturation of DC by regulating miR-221. The HCC cell line was co-cultured with immature DC from mice bone marrow, and the levels of CD86 and CD40 was detected by FCM. Our results showed that myrothecine A could rescue miR-221-induced cell proliferation and influence the protein level of p27 by inhibiting the expression of miR-221. In addition, myrothecine A could enhance the expression of CD86 and CD40 by reversing the function of miR-221. Therefore, myrothecine A may be acted as an anti-tumor drug to promote the maturation of DC in the microenvironment of hepatocellular carcinoma.