Berdel W E
Department of Medicine I, Technische Universitaet, Munich, Federal Republic of Germany.
Lipids. 1987 Nov;22(11):970-3. doi: 10.1007/BF02535567.
This review covers the work of our laboratory on the antineoplastic activity of some ether lipids and derivatives that are related to platelet-activating factor (PAF). Various 1-O-alkyl lysophospholipid derivatives (ALP) show therapeutic activity in mouse transplant tumor models and in metastatic 3-Lewis lung carcinoma in vivo. However, certain autochthonous mouse leukemias and radiation-induced lymphomas are resistant to ALP treatment. The therapeutic effects of these compounds are partially due to the activation of cytotoxic macrophages and direct cytotoxicity. Approximately 20 ether lipids and derivatives were tested for direct cytotoxicity in cells from human solid tumors and leukemias using [3H]thymidine uptake, trypan blue dye exclusion, human tumor clonogenic assays (HTCA) and cell morphology as criteria. Certain ALP, thioether lysophospholipid-derivatives (TLP), ether-linked lipoidal amines, sn-2 analogs of PAF, and conjugates of ether lipids and cytosine arabinoside were found cytotoxic in a dose- and time-dependent fashion. Cytotoxicity of some of the ether lipids tested is based on destruction of cell membranes. Structure-activity studies were performed to better understand the mechanisms leading to accumulation and cytotoxicity of ALP. Comparative studies with normal bone marrow cells and leukemic blasts from humans revealed preferential anti-leukemic cytotoxicity of three ether lipids.
本综述涵盖了我们实验室对一些与血小板活化因子（PAF）相关的醚脂及其衍生物的抗肿瘤活性的研究工作。各种1-O-烷基溶血磷脂衍生物（ALP）在小鼠移植瘤模型和体内转移性3-刘易斯肺癌中显示出治疗活性。然而，某些自发的小鼠白血病和辐射诱导的淋巴瘤对ALP治疗具有抗性。这些化合物的治疗效果部分归因于细胞毒性巨噬细胞的激活和直接细胞毒性。使用[3H]胸苷摄取、台盼蓝染料排除法、人肿瘤克隆形成试验（HTCA）和细胞形态学作为标准，对大约20种醚脂及其衍生物在人实体瘤和白血病细胞中的直接细胞毒性进行了测试。某些ALP、硫醚溶血磷脂衍生物（TLP）、醚连接的类脂胺、PAF的sn-2类似物以及醚脂与阿糖胞苷的缀合物在剂量和时间依赖性方式下具有细胞毒性。所测试的一些醚脂的细胞毒性基于细胞膜的破坏。进行了构效关系研究，以更好地理解导致ALP积累和细胞毒性的机制。对来自人类的正常骨髓细胞和白血病母细胞的比较研究揭示了三种醚脂具有优先的抗白血病细胞毒性。
