Ginsenoside Rh2 inhibits prostate cancer cell growth through suppression of microRNA-4295 that activates CDKN1A.

OBJECTIVES: Ginsenoside Rh2 (GRh2) has demonstrative therapeutic effects on a variety of diseases, including some tumours. However, the effects of GRh2 on prostate cancer (PC) cell growth remain unknown, and were, thus, addressed in the present study.

MATERIALS AND METHODS: PC3 and DU145 PC cell lines were exposed to GRh2. Cell proliferation was assessed in an MTT assay and by BrdU incorporation. Apoptosis of the cells were assessed by TUNEL staining. Total RNA was assessed by RT-qPCR. Protein levels were assessed by Western blotting. Bioinformatics and dual luciferase reporter assay were applied to determine the functional binding of miRNA to mRNA of target gene.

RESULTS: GRh2 dose-dependently decreased PC cell proliferation, but did not alter cell apoptosis. Mechanistically, GRh2 dose-dependently increased the protein, but not mRNA of a cell-cycle suppressor CDKN1A in PC cells, suggesting the presence of microRNA (miRNA)-mediated protein translation control of CDKN1A by GRh2. In all candidate miRNAs that bind to 3'-UTR of CDKN1A, miR-4295 was specifically found to be suppressed dose-dependently by GRh2 in PC cells. Moreover, miR-4295 bound CDKN1A to suppress its protein translation. Furthermore, cell proliferation in PC cells that overexpressed miR-4295 did not alter in response to GRh2.

CONCLUSIONS: GRh2 may inhibit PC cell growth through suppression of microRNA-4295 that activates CDKN1A.