[In vitro study of the effects of CDA-II combined with cAMP on apoptosis induction in retinoic acid resistant acute promyelocytic leukemia cells].
OBJECTIVE
To investigate the effects of CDA-II alone or combined with cAMP on the retinoic acid (RA)-resistant acute promyelocytic leukemia (APL) cells.


METHODS
The RA-resistant cell line NB4-R2 was used as an in vitro model and treated with CDA-II alone or in combination with cAMP. Cell apoptosis was assessed by morphology observation, distribution of cellular DNA contents and sub-G1 cell population. The level of Bcl-2 was detected by flow cytometry, DNA "ladder" was detected by agarose-electrophoresis.


RESULTS
CDA-II could induce NB4-R2 cell apoptosis through decreasing the level of cellular anti-apoptotic protein Bcl-2. cAMP could significantly enhance the role of CDA-II. Bcl-2 positive cell rates decreased to (15.1 +/- 4.8)% and (7.3 +/- 2.9)% in NB4-R2 cells treated with 1 mg/ml CDA-II plus 100 micromol/L cAMP for 48 h and 72 h, respectively. While 100 micromol/L of cAMP could decrease Bcl-2 positive NB4-R2 cells from (92.0 +/- 0.6)% to (75.3 +/- 2.0)%.


CONCLUSIONS
CDA-II combined with cAMP could exert potent apoptotic effect on RA-resistant APL cells.
Jia
Pei-Min
PM
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Pan
Xiao-Rong
XR
Xiao
Shu
S
Li
Dong
D
Wang
Zhen-Yi
ZY
Tong
Jian-Hua
JH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D039521:CD11c Antigen / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000473:pathology*; D010455:Peptides / Q000494:pharmacology*; D010648:Phenylacetates / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
D039521:CD11c Antigen; D010455:Peptides; D010648:Phenylacetates; D019253:Proto-Oncogene Proteins c-bcl-2; C480340:cell differentiation agent II; D014212:Tretinoin; D000242:Cyclic AMP