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Cyclic polylactate inhibited growth of cloned leukemic cells through reducing glycolytic enzyme activities.

Identifieur interne : 002F16 ( Main/Curation ); précédent : 002F15; suivant : 002F17

Cyclic polylactate inhibited growth of cloned leukemic cells through reducing glycolytic enzyme activities.

Auteurs : Tomonori Harada [Japon] ; Masaya Nagasu ; Isao Tsuboi ; Morimichi Koshinaga ; Hitoshi Kanno ; Shin Aizawa

Source :

RBID : pubmed:16012737

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Abstract

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.

PubMed: 16012737

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<term>Bone Marrow Cells (cytology)</term>
<term>Bone Marrow Cells (drug effects)</term>
<term>Bone Marrow Cells (metabolism)</term>
<term>Caspase 3</term>
<term>Caspase 9</term>
<term>Caspases (metabolism)</term>
<term>Cell Line, Tumor</term>
<term>Cell Proliferation (drug effects)</term>
<term>Chromatography, Liquid (methods)</term>
<term>Clone Cells (drug effects)</term>
<term>Culture Media, Conditioned (chemistry)</term>
<term>Dose-Response Relationship, Drug</term>
<term>Enzymes (metabolism)</term>
<term>Glucosephosphate Dehydrogenase (antagonists & inhibitors)</term>
<term>Glucosephosphate Dehydrogenase (metabolism)</term>
<term>Glycolysis</term>
<term>HeLa Cells</term>
<term>Hexokinase (antagonists & inhibitors)</term>
<term>Hexokinase (metabolism)</term>
<term>Humans</term>
<term>Lactates (analysis)</term>
<term>Lactates (chemical synthesis)</term>
<term>Lactates (pharmacology)</term>
<term>Leukemia (enzymology)</term>
<term>Leukemia (pathology)</term>
<term>Mass Spectrometry (methods)</term>
<term>Membrane Proteins (analysis)</term>
<term>Phosphogluconate Dehydrogenase (antagonists & inhibitors)</term>
<term>Phosphogluconate Dehydrogenase (metabolism)</term>
<term>Polymers (analysis)</term>
<term>Polymers (chemical synthesis)</term>
<term>Polymers (pharmacology)</term>
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<term>Stromal Cells (drug effects)</term>
<term>Stromal Cells (metabolism)</term>
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<term>Caspase-9</term>
<term>Caspases (métabolisme)</term>
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<term>Cellules de la moelle osseuse ()</term>
<term>Cellules de la moelle osseuse (cytologie)</term>
<term>Cellules de la moelle osseuse (métabolisme)</term>
<term>Cellules stromales ()</term>
<term>Cellules stromales (cytologie)</term>
<term>Cellules stromales (métabolisme)</term>
<term>Chromatographie en phase liquide ()</term>
<term>Clones cellulaires ()</term>
<term>Enzymes (métabolisme)</term>
<term>Glucose 6-phosphate dehydrogenase (antagonistes et inhibiteurs)</term>
<term>Glucose 6-phosphate dehydrogenase (métabolisme)</term>
<term>Glycolyse</term>
<term>Hexokinase (antagonistes et inhibiteurs)</term>
<term>Hexokinase (métabolisme)</term>
<term>Humains</term>
<term>Lactates (analyse)</term>
<term>Lactates (pharmacologie)</term>
<term>Lactates (synthèse chimique)</term>
<term>Leucémies (anatomopathologie)</term>
<term>Leucémies (enzymologie)</term>
<term>Lignée cellulaire tumorale</term>
<term>Milieux de culture conditionnés ()</term>
<term>Phosphogluconate dehydrogenase (antagonistes et inhibiteurs)</term>
<term>Phosphogluconate dehydrogenase (métabolisme)</term>
<term>Polymères (analyse)</term>
<term>Polymères (pharmacologie)</term>
<term>Polymères (synthèse chimique)</term>
<term>Prolifération cellulaire ()</term>
<term>Protéines membranaires (analyse)</term>
<term>Relation dose-effet des médicaments</term>
<term>Spectrométrie de masse ()</term>
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<term>Membrane Proteins</term>
<term>Polymers</term>
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<term>Enzymes</term>
<term>Glucosephosphate Dehydrogenase</term>
<term>Hexokinase</term>
<term>Phosphogluconate Dehydrogenase</term>
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<term>Polymers</term>
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<term>Lactates</term>
<term>Polymères</term>
<term>Protéines membranaires</term>
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<term>Chromatography, Liquid</term>
<term>Mass Spectrometry</term>
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<term>Caspases</term>
<term>Cellules de la moelle osseuse</term>
<term>Cellules stromales</term>
<term>Enzymes</term>
<term>Glucose 6-phosphate dehydrogenase</term>
<term>Hexokinase</term>
<term>Phosphogluconate dehydrogenase</term>
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<term>Caspase-9</term>
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<term>Cellules de la moelle osseuse</term>
<term>Cellules stromales</term>
<term>Chromatographie en phase liquide</term>
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<term>Glycolyse</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Milieux de culture conditionnés</term>
<term>Prolifération cellulaire</term>
<term>Relation dose-effet des médicaments</term>
<term>Spectrométrie de masse</term>
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<front>
<div type="abstract" xml:lang="en">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.</div>
</front>
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