Document Detail

Cyclic polylactate inhibited growth of cloned leukemic cells through reducing glycolytic enzyme activities.
MedLine Citation:
PMID:  16012737     Owner:  NLM     Status:  MEDLINE    
A novel supramolecular oligomer, cyclic polylactate (CPL) that was originally discovered in the culture medium of HeLa-S tumor cells, reportedly inhibits the growth of FM3A ascites tumor cells by inhibiting enzymes involved in the glycolytic pathway. We synthesized CPL containing 3- to 13-mers by prolonged heating and rapidly mixing a carbohydrate compound of the L-lactic acid monomer (C(3)H(6)O(3)) under decreased pressure, and studied its effects on the growth of the cloned leukemic cell, TF-1. CPL inhibited the growth of TF-1 cells and induced 7A6 antigen, which is expressed by cells undergoing apoptosis, on the surface of TF-1 cells. In addition, caspase 3, 8 and 9 activities of TF-1 cells were increased after exposure to CPL, indicating that CPL induces apoptotic changes in TF-1. Among the 6 glycolytic enzymes examined in this study, the activities of PFK and HK, induced by CPL, decreased. Interestingly, CPL was detected in conditioned medium of the stromal cell line, LS801, obtained from human bone marrow. This conditioned medium inhibited the growth of TF-1 cells, and induced the expression of 7A6 antigen. These findings suggest that CPL will be a useful chemotherapeutic agent against leukemia.
Tomonori Harada; Masaya Nagasu; Isao Tsuboi; Morimichi Koshinaga; Hitoshi Kanno; Shin Aizawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology reports     Volume:  14     ISSN:  1021-335X     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-13     Completed Date:  2005-09-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  501-5     Citation Subset:  IM    
Department of Anatomy, Nihon University School of Medicine, 30-1 Ohyaguchi-kami-machi, Itabashi-ku, Tokyo 173-8610, Japan.
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MeSH Terms
Bone Marrow Cells / cytology,  drug effects,  metabolism
Caspase 3
Caspase 9
Caspases / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Chromatography, Liquid / methods
Clone Cells / drug effects
Culture Media, Conditioned / chemistry
Dose-Response Relationship, Drug
Enzymes / metabolism*
Glucosephosphate Dehydrogenase / antagonists & inhibitors,  metabolism
Hela Cells
Hexokinase / antagonists & inhibitors,  metabolism
Lactates / analysis,  chemical synthesis,  pharmacology*
Leukemia / enzymology,  pathology
Mass Spectrometry / methods
Membrane Proteins / analysis
Phosphogluconate Dehydrogenase / antagonists & inhibitors,  metabolism
Polymers / analysis,  chemical synthesis,  pharmacology*
Stromal Cells / cytology,  drug effects,  metabolism
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Enzymes; 0/Lactates; 0/Membrane Proteins; 0/Polymers; 0/antigen 7A6; 0/cyclic polylactate; EC Dehydrogenase; EC Dehydrogenase; EC; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases

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