The p53-mediated cell cycle regulation is a potential mechanism for emodin-suppressing osteosarcoma cells

Background: As the most common primary bone cancer, the therapy of osteosarcoma requires further study. An anthraquinone derivative, emodin, has been found to have anticancer potential. We proposed that emodin suppresses osteosarcoma by cell cycle regulation mediated by p53. Methods: This study determined the effect of emodin on viability and apoptosis of 6 osteosarcoma cell lines (p53 null cells MG63, G292, and A-673; p53 mutated cells HOS and SK-PN-DW; p53 expressing cells U2OS and 2 osteoblast cell lines), then knockdown p53 in U2OS, and observed the impacts of emodin on p53, p21, cyclin proteins, and cell cycle. Results: High dose emodin (40-160 mu M) induced cell death and apoptosis of all the cell lines; medium dose emodin (20 mu M) preferentially inhibited osteosarcoma cells; low dose emodin (1-10 mu M) preferentially inhibited p53 expressing osteosarcoma cells. Emodin dose -dependently inhibited p53 and p21 in U2OS. Emodin at 10 mu M decreased the expression of Cdk2, E2F, and Cdk1; and increased RB but had no effects on cyclin E and cyclin B. The knockdown of p53 almost eliminated all the impacts of 10 mu M emodin on cell cycle proteins. Conclusions: Emodin suppresses U2OS by p53 -mediated cell cycle regulation.