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

被引:25
作者
Gao, F. [2 ]
Tang, Q. [3 ]
Yang, P. [2 ]
Fang, Y. [2 ]
Li, W. [4 ]
Wu, Y. [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Key Lab Cell Differentiat & Apoptosis, Dept Pathophysiol,Natl Minist Educ, Shanghai 200025, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp Affiliated 3, Shanghai 200025, Peoples R China
[3] Shanghai Acad Agr Sci SAAS, Inst Edible Fungi, Shanghai, Peoples R China
[4] Wenzhou Med Coll, Sch Life Sci, Zhejiang Prov Key Lab Med Genet, Wenzhou, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Oridonin; apoptosis; ROS; leukemia; differentiation; OXYGEN SPECIES ROS; ANTITUMOR-ACTIVITY; BINDING-PROTEINS; RAR-ALPHA; DITERPENOIDS; INHIBITION; MATURATION; MECHANISM;
D O I
10.1111/j.1751-553X.2009.01147.x
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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 RAR alpha, C/EBP epsilon or C/EBP beta. This is the first report to show that RAR alpha could be accumulated by Ori which may be useful as a probe to investigate the mechanism of RAR alpha catabolism. These results suggest that Ori is a potential candidate for acute promyelocytic leukemia cancer therapy.
引用
收藏
页码:E114 / E122
页数:9
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