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

Oncol Rep. 2005 Aug;14(2):501-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / 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
  • Glucosephosphate Dehydrogenase / metabolism
  • Glycolysis
  • HeLa Cells
  • Hexokinase / antagonists & inhibitors
  • Hexokinase / metabolism
  • Humans
  • Lactates / analysis
  • Lactates / chemical synthesis
  • Lactates / pharmacology*
  • Leukemia / enzymology
  • Leukemia / pathology
  • Mass Spectrometry / methods
  • Membrane Proteins / analysis
  • Phosphogluconate Dehydrogenase / antagonists & inhibitors
  • Phosphogluconate Dehydrogenase / metabolism
  • Polymers / analysis
  • Polymers / chemical synthesis
  • Polymers / pharmacology*
  • Stromal Cells / cytology
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism

Substances

  • Culture Media, Conditioned
  • Enzymes
  • Lactates
  • Membrane Proteins
  • Polymers
  • antigen 7A6
  • cyclic polylactate
  • Phosphogluconate Dehydrogenase
  • Glucosephosphate Dehydrogenase
  • Hexokinase
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9
  • Caspases