[Effect of N-tosyl-L-phenylalnylchloromethyl ketone and dexamethasone on expression of nuclear transcription factor-kappaB in childhood acute lymphoblastic leukemia and its significance].

Abstract

In order to investigate the effect of N-tosyl-L-phenylalnylchloromethyl ketone (TPCK) and dexamethasone (Dex) on expression of nuclear transcription factor-kappaB (NF-kappaB) in childhood acute lymphoblastic leukemia (ALL) and its significance, so as to provide the experimental basis for corresponding clinical treatment of ALL, in which NF-kappaB is taken as a target. The biotin-streptavidin method was used to detect the expression of NF-kappaB P65 protein and the effects of TPCK and Dex at clinically relevant dosage on activity of NF-kappaB P65 protein in 20 childhood ALL patients. The results indicated that the expression of NF-kappaB P65 protein was strongly diminished and reached to negative level at 2 hours by treatment with 40 micromol/L TPCK, the positive expression of NF-kappaB P65 protein was (2.5 +/- 1.6)%. TPCK had a time-dependent inhibitory effect on ALL cells cultured in vitro. The expression of NF-kappaB P65 protein in ALL cells was strongly inhibited by clinically relevant concentration of dexamethasone 5.0 microg/ml for 24 hours in vitro. The positive expression was (25.0 +/- 3.0)%, there was significant difference, as compared with untreated ALL cells (T=55, P<0.01). It is concluded that TPCK and Dex can inhibit NF-kappaB activity. Inhibition of NF-kappaB activity may be one of the effect mechanism of dexamethasone on ALL cells. Inhibition of NF-kappaB conduction pathway may have a significant value in childhood ALL treatment.

• Authors: Qig An, Tian-Yang Xue, Wei Xu, Ji-Zhao Gao, Yi Wu, Chun-Pin Xu
• Journal: Zhongguo shi yan xue ye xue za zhi (Zhongguo Shi Yan Xue Ye Xue Za Zhi) Vol. 15 Issue 2 Pg. 399-403 (Apr 2007) ISSN: 1009-2137 [Print] China
• PMID: 17493356 (Publication Type: English Abstract, Journal Article)

Chemical References

• NF-kappa B
• Protein Synthesis Inhibitors
• Tosylphenylalanyl Chloromethyl Ketone
• Dexamethasone

Topics

• Bone Marrow Cells (pathology)
• Cells, Cultured
• Child
• Child, Preschool
• Dexamethasone (pharmacology)
• Female
• Humans
• Infant
• Leukocytes, Mononuclear (pathology)
• Male
• NF-kappa B (biosynthesis, genetics)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (metabolism, pathology)
• Protein Synthesis Inhibitors (pharmacology)
• Tosylphenylalanyl Chloromethyl Ketone (pharmacology)
• Tumor Cells, Cultured