[In vitro study of the effects of arsenic trioxide combined with 8-CPT-cAMP on differentiation induction in retinoic acid resistant acute promyelocytic leukemia cells].

Abstract

OBJECTIVE:

To investigate the potential effects of arsenic trioxide (As(2)O(3)) combined with 8-(4-chlorophenylthio) adenosine 3', 5'-cyclic monophosphate (8-CPT-cAMP) on the retinoic acid (RA)-resistant acute promyelocytic leukemia (APL) cells.

METHODS:

The RA resistant APL cell lines NB4-R1 and NB4-R2 were used as in vitro models. The effect of As(2)O(3) and/or 8-CPT-cAMP was evaluated according to cellular morphology, cell surface antigen and nitroblue-tetrazolium (NBT) assay. Meanwhile, immunofluorescence analysis and Western blot assay were used to detect the degradation of PML-RAR alpha fusion protein and the change of several key cell cycle regulatory proteins in these cells before and after the treatment.

RESULTS:

Low dose of As(2)O(3) (0.25 micromol/L) synergized with 8-CPT-cAMP (200 micromol/L) in inducing differentiation of NB4-R1 and NB4-R2 cells, while neither of these two drugs alone could induce differentiation of these cells. In addition, 8-CPT-cAMP was able to inhibit the cell growth by modulating the expression of some important cell cycle regulators and to facilitate the As(2)O(3)-mediated degradation of PML-RAR alpha fusion protein.

CONCLUSIONS:

As(2)O(3) combined with 8-CPT-cAMP could induce differentiation of RA-resistant APL cells.

• Authors: Qi Zhu, Yun Yu, Pei-min Jia, Xun Cai, Sai-juan Chen, Zhu Chen, Zhen-yi Wang, Jian-hua Tong
• Journal: Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi (Zhonghua Xue Ye Xue Za Zhi) Vol. 24 Issue 1 Pg. 6-9 (Jan 2003) ISSN: 0253-2727 [Print] China
• PMID: 12679001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Arsenicals
• Oxides
• Thionucleotides
• 8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
• Tretinoin
• Cyclic AMP
• Arsenic Trioxide

Topics

• Antineoplastic Agents (pharmacology)
• Arsenic Trioxide
• Arsenicals (pharmacology)
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Cyclic AMP (analogs & derivatives, pharmacology)
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm
• Drug Synergism
• Humans
• Leukemia, Promyelocytic, Acute (pathology)
• Oxides (pharmacology)
• Thionucleotides (pharmacology)
• Tretinoin (pharmacology)