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Proteomic approach to studying the cytotoxicity of YC‐1 on U937 leukemia cells and antileukemia activity in orthotopic model of leukemia mice
Author(s) -
Chung JingGung,
Yang JaiSing,
Huang LiJiau,
Lee FangYu,
Teng CheMing,
Tsai ShengChung,
Lin KueiLi,
Wang ShuFang,
Kuo ShengChu
Publication year - 2007
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200700200
Subject(s) - apoptosis , leukemia , microbiology and biotechnology , spleen , biology , chemistry , tunel assay , viability assay , biochemistry , immunology
To evaluate the effects of YC‐1 on leukemia cell lines, PI incorporation was used to determine cell viability. YC‐1 induced a dose‐ and time‐dependent decrease in viability and apoptosis in YC‐1‐treated U937 cells. YC‐1‐induced apoptosis is a cyclic guanosine monophosphate (cGMP)‐independent pathway. Proteomic analysis showed that the altered proteins include the significant regulation of HSP70, chaperonin, ATP synthase beta chains, and Chain F. Western blotting and immuno‐cytochemistry stain showed that YC‐1 treatment caused a time‐dependent increase in cytosolic Cytochrome c , pro‐caspase‐9, Apaf‐1, and the activation of caspase‐9 and ‐3. Importantly, the in vivo antileukemia effects of YC‐1 were evaluated in BALB/c mice inoculated with WEHI‐3B orthotopic model. YC‐1 enhanced survival rate and prevented the body weight loss in leukemia mice. The enlargement of spleen and lymph nodes were reduced in YC‐1 treated than that in leukemia mice. H‐E stain of spleen sections revealed that infiltration of immature myeloblastic cells into red pulp was reduced in YC‐1‐treated group. The apoptotic cells of splenocyte were significantly increased in YC‐1 treated than that in leukemia mice by Tdt‐mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. Taken together, we conclude that YC‐1 acted against U937 cells in vitro via a mitochondrial‐dependent apoptosis pathway, and in orthotopic leukemia model, YC‐1 administered antileukemia activity.