Apoptosis inducing and differentiation enhancement effect of oridonin on the all-trans-retinoic acid-sensitive and -resistant acute promyelocytic leukemia cells.

We investigated the effects of oridonin (Ori), a diterpenoid isolated from Rabdosia rubescens, on apoptosis and differentiation of all-trans-retinoic acid (ATRA)-sensitive (NB4) and ATRA-resistant (NB4-R1) cells. The results showed that reactive oxygen species initiates Ori-induced apoptosis. In addition, we found that neither Ori nor ATRA (10 nM) alone induced marked cell differentiation, while co-treatment of these two compounds can induce differentiation of NB4 and NB4-R1 cells which was accompanied by increased RARalpha, C/EBPepsilon or C/EBPbeta. This is the first report to show that RARalpha could be accumulated by Ori which may be useful as a probe to investigate the mechanism of RARalpha catabolism. These results suggest that Ori is a potential candidate for acute promyelocytic leukemia cancer therapy.