Sidoti C, Principe P, Vandamme B, Broquet C, Braquet P
Institut Henri Beaufour Research Laboratories, Les Ulis, France.
Int J Cancer. 1992 Jul 9;51(5):712-7. doi: 10.1002/ijc.2910510509.
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.
烷基溶血磷脂是天然存在的2-溶血磷脂酰胆碱的类似物，据报道具有选择性体外/体内抗肿瘤活性。已发现它们对多种动物和人类肿瘤细胞系具有抗增殖作用。我们已经对两种新合成的氮杂烷基溶血磷脂（AALP），即BN52205和BN52211，对源自结肠腺癌的人肿瘤细胞系HT29的细胞生长抑制活性进行了表征。我们使用了3种不同的流式细胞术方法来研究细胞周期的哪个阶段对这两种AALP的抗增殖活性最敏感。通过应用5'-溴-2-脱氧尿苷掺入与DNA含量的双参数分析，我们能够证明这两种AALP不会干扰细胞周期的S期。同时测量分离的HT29细胞核中的总核蛋白与DNA含量，使我们能够排除细胞周期M期的阻滞。最后，生长速率分析使我们能够表明，这两种新AALP的细胞生长抑制活性的特征是多个“终点”，因为药物的作用导致G1期阻滞，从S期末期到G2期的转变减缓，随后HT29细胞在细胞周期的G2期积累。
