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Cytostatic activity of new synthetic anti‐tumor aza‐alkyllysophospholipids
Author(s) -
Sidoti Carole,
Principe Paola,
Vandamme Benedicte,
Broquet Colette,
Braquet Pierre
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910510509
Subject(s) - cell cycle , in vivo , cell culture , in vitro , dna synthesis , lysophosphatidylcholine , microbiology and biotechnology , dna , biology , cell , chemistry , adenocarcinoma , biochemistry , genetics , cancer , phospholipid , membrane , phosphatidylcholine
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 anti‐proliferative 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 anti‐proliferative 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 ee 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 G 1 block, in a slow‐down of the transition from late S to G 2 followed by an accumulation of HT29 cells in the G 2 phase of the cell cycle. © 1992 Wifey‐Liss, Inc.