Cytostatic activity of new synthetic anti-tumor aza-alkyllysophospholipids.
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.
Sidoti
C
C
Institut Henri Beaufour Research Laboratories, Les Ulis, France.
Principe
P
P
Vandamme
B
B
Broquet
C
C
Braquet
P
P
D000230:Adenocarcinoma / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008246:Lysophospholipids / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D008246:Lysophospholipids; C072522:BN 52205; C072525:BN 52211