Oridonin is an orally available
drug isolated from
Traditional Chinese Medicine. Previous studies with
oridonin have demonstrated broad-spectrum anticancer activity in a variety of
cancer types. However, the effect of
oridonin in
uveal melanoma has not been addressed. In this study, we aimed to investigate whether
oridonin elicited anticancer activity and its underlying mechanism in human
uveal melanoma cells. We demonstrated that
oridonin potently reduced cell viability, induced apoptosis and inhibited clonogenic survival and growth with single digit micromolar concentrations in
uveal melanoma OCM-1 and MUM2B cell lines. We found that
oridonin markedly increased the expression of proapoptotic Bcl-2 family
protein Bim in
uveal melanoma cells, and knockdown Bim by
small interfering RNA significantly attenuated
oridonin-induced cell death, indicating an essential role of Bim in
oridonin-mediated anticancer activity. Additionally, we observed that
oridonin suppressed
Fatty Acid Synthase (FAS) expression in
uveal melanoma cells, and enforced FAS expression by
insulin partially rescued the cells from
oridonin-induced apoptosis, showing that inhibition of FAS also contributed to
oridonin-mediated apoptosis. Taken together, we reported that
oridonin displays potent anticancer effect against
uveal melanoma cells through upregulation of Bim and inhibition of FAS. Since
oridonin is a popular
anticancer agent, our study therefore may have translational implication on the management of patients with
uveal melanoma.