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.
Gao
F
F
NO.3 People's Hospital affiliated to Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai, China.
Tang
Q
Q
Yang
P
P
Fang
Y
Y
Li
W
W
Wu
Y
Y
D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology; D018168:Receptors, Retinoic Acid / Q000502:physiology; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin / Q000494:pharmacology*
D045786:Diterpenes, Kaurane; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C011959:oridonin; D014212:Tretinoin