Cytostatic activity of new synthetic anti-tumor aza-alkyllysophospholipids

Int J Cancer. 1992 Jul 9;51(5):712-7. doi: 10.1002/ijc.2910510509.

Abstract

Alkyllysophospholipids are analogues of the naturally occurring 2-lysophosphatidylcholine which have been reported to have selective in vitro/in vivo anti-tumor activity. Their antiproliferative effect has been found against a variety of animal and human tumor cell lines. We have characterized the cytostatic activity of 2 newly synthetized aza-alkyllysophospholipids (AALPs), the BN52205 and the BN52211, on a human tumor cell line derived from a colon adenocarcinoma, the HT29. We used 3 different flow cytometric approaches to study which phase of the cell cycle was the most sensitive to the antiproliferative activity of the 2 AALPs. By applying the biparametric analysis of 5'-bromo-2-deoxyuridine incorporation vs. DNA content we have been able to demonstrate that the 2 AALPs do not interfere with the S phase of the cell cycle. The simultaneous measurement of total nuclear protein vs. DNA content in isolated HT29 nuclei enabled us to exclude a block in the M phase of the cell cycle. Finally, stathmokinetic analysis enabled us to show that cytostatic activity of the 2 new AALPs is characterized by multiple "terminal points" as the drugs' action results in a G1 block, in a slow-down of the transition from late S to G2 followed by an accumulation of HT29 cells in the G2 phase of the cell cycle.

MeSH terms

  • Adenocarcinoma / pathology*
  • Antineoplastic Agents / pharmacology*
  • Cell Division / drug effects
  • Colonic Neoplasms / pathology*
  • DNA, Neoplasm / biosynthesis
  • Flow Cytometry
  • G1 Phase / drug effects*
  • G2 Phase / drug effects*
  • Humans
  • Kinetics
  • Lysophospholipids / chemistry
  • Lysophospholipids / pharmacology*
  • Molecular Structure
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • DNA, Neoplasm
  • Lysophospholipids
  • BN 52205
  • BN 52211