[Acute promyelocytic leukemia cell differentiation induced by tanshinone II A and its molecular mechanism].
OBJECTIVE
To investigate APL cell differentiation induced by tanshinone II (Tan II A) and its molecular mechanism.


METHODS
In vitro incubation of NB4 cells with Tan II A at the concentration of 0.5 microg/ml for 5 days, the cell differentiation was observed by cytomorphology, and nitroblue tetrazolium (NBT) test. Cell cycle, membrane CD(33), CD(11b) antigens and gene expressions (c-myc, c-fos, p53 and bcl-2) were analysed by flow cytometry.


RESULTS
(91.3 +/- 2.1)% of NB4 cells were induced into morphologically and functionally more differentiated cells including 0.26 of myelocytes and metamyelocytes, and 0.68 of band form and neutrophils. Cell growth curve showed that growth of NB4 cells were inhibited. NBT reduction was significantly increased. Expression of CD(33) decreased and CD(11b) increased. The degrees of cell differentiation and growth inhibition induced by Tan II A or ATRA were no difference. Flow cytometry analysis showed that Tan II A arrested NB4 cell in G(0)/G(1) phase, inhibited cellular DNA synthesis, down-regulated c-myc and bcl-2 genes expression, and up-regulated c-fos and p53 genes expression.


CONCLUSIONS
Tan II A can induce differentiation and growth inhibition of NB4 cells. Its possible molecular mechanism might relate to modulation of gene expressions associated proliferation and differentiation, and to inhibition of DNA synthesis.
Liang
Y
Y
Department of Hematology, First Affiliated Hospital of West China University of Medical Sciences, Chengdu 610041, China.
Yang
Y
Y
Yuan
S
S
Meng
W
W
Liu
T
T
Jia
Y
Y
D045784:Abietanes; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016158:Genes, p53; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use
D045784:Abietanes; D010616:Phenanthrenes; C021751:tanshinone