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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.

Abstract
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.
AuthorsJing-Gung Chung, Jai-Sing Yang, Li-Jiau Huang, Fang-Yu Lee, Che-Ming Teng, Sheng-Chung Tsai, Kuei-Li Lin, Shu-Fang Wang, Sheng-Chu Kuo
JournalProteomics (Proteomics) Vol. 7 Issue 18 Pg. 3305-17 (Sep 2007) ISSN: 1615-9853 [Print] Germany
PMID17849408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Indazoles
  • 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
Topics
  • Animals
  • Apoptosis (drug effects)
  • Blotting, Western
  • Electrophoresis, Agar Gel
  • Electrophoresis, Gel, Two-Dimensional
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Indazoles (pharmacology)
  • Leukemia, Experimental (pathology)
  • Male
  • Mass Spectrometry
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • U937 Cells

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