Relationship between the antileukemic activity of L-asparaginase and Asn level around leukemic cells.
- Author:
Ben-Shang LI
1
;
Chang-Ying LUO
;
Ying-Yi HE
;
Hua JIANG
;
Long-Jun GU
Author Information
- Publication Type:Journal Article
- MeSH: Asparaginase; pharmacology; Asparagine; analysis; Cell Line, Tumor; Cell Proliferation; drug effects; Chromatography, High Pressure Liquid; Humans; Leukemia; drug therapy; metabolism; pathology; Precursor Cell Lymphoblastic Leukemia-Lymphoma; drug therapy
- From: Chinese Journal of Contemporary Pediatrics 2010;12(7):557-562
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the antileukemic activity of L-asparaginase through determining the changes of 4 kinds of amino acids (Asn, Aspa, Glu and Gln) in cell culture medium.
METHODSFollowing L-Asp treatment with designed concentrations and duration, the IC50 (inhibitory concentration 50%) of 8 kinds of common leukemia cell lines (U937, HL-60, Jurkat, NB4, THP-1, Namalwa, Karpass299, K562) were determined by CCK-8 assay. The changes of the 4 kinds of amino acids mentioned above were detected by high performance liquid chromatography (HPLC).
RESULTSThe asparagines in cell culture medium were rapidly exhausted when treated with 0.01 U/mL L-Asp for 4 hrs or 1 U/mL L-Asp for 5 minutes. There were significant differences in the sensitivities to L-Asp of different leukemia cell lines. The sensitivities to L-Asp of various cell lines were dose-dependent. Low concentration of L-Asp resulted in a low IC50 and the IC50 increased following the L-Asp concentration increased.
CONCLUSIONSDifferent leukemia cell lines have different sensitivities to L-Asp, suggesting that exhaustion of asparagines around leukemia cells could not reflect the treatment efficacy of L-Asp. L-Asp antileukemic activity is dose-dependent, which suggests the importance of high-dose L-Asp on childhood acute lymphoblastic leukemia.