PHOSPHOLIPID ANALOG HEXADECYLPHOSPHOCHOLINE INHIBITS PROLIFERATION AND PHOSPHATIDYLCHOLINE BIOSYNTHESIS OF HUMAN EPIDERMAL-KERATINOCYTES IN-VITRO

被引:26
作者
DETMAR, M
GEILEN, CC
WIEDER, T
ORFANOS, CE
REUTTER, W
机构
[1] FREE UNIV BERLIN,MED CTR STEGLITZ,DEPT DERMATOL,W-1000 BERLIN,GERMANY
[2] FREE UNIV BERLIN,INST MOLEK & BIOCHEM,W-1000 BERLIN,GERMANY
关键词
HEXADECYLPHOSPHOCHOLINE; PHOSPHATIDYLCHOLINE; ANTINEOPLASTIC ACTIVITY; PSORIASIS;
D O I
10.1111/1523-1747.ep12373109
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
The alkylphospholipid hexadecylphosphocholine (HePC), member of a new class of antineoplastic drugs, has been previously shown to exert cytotoxic effects on neoplastic cell lines in vitro, and a selective antineoplastic activity has been reported after topical application of HePC in vivo, in particular on skin metastases of human mammary carcinomas. Preliminary observations suggest that HePC might also be benefical in the treatment of non-neoplastic skin diseases characterized by epidermal hyperplasia such as psoriasis. Therefore, we investigated whether HePC might inhibit the proliferation of normal human keratinocytes, and whether its effects might be dependent upon the proliferative status of the treated cells. Moreover, its effects on phosphatidylcholine biosynthesis were studied in keratinocytes. HePC dose-dependently decreased cell numbers, thymidine incorporation, and protein synthesis when applied during the growth phase of keratinocytes grown in serum-free medium, with a minimal inhibitory dose of 10(-7) mol/l for thymidine incorporation, 3 X 10(-7) mol/l for cell numbers, and 10(-6) mol/l for S-35-methionine incorporation. No major differences were observed when keratinocytes were grown under high-Ca++ conditions. In contrast, slowly proliferating confluent keratinocyte cultures showed growth inhibition only after 10(-4) mol/l HePC. Phosphatidylcholine biosynthesis was dose-dependently inhibited by HePC with a half inhibitory concentration of 3 X 10(-6) mol/l, and with translocation of the rate-limiting enzyme, CTP:phosphocholine cytidylyltransferase, to the cytosol, where the enzyme is inactive. These data show a pronounced antiproliferative effect of HePC also on proliferating non-malignant keratinocytes, and are compatible with its possible action on hyperproliferative skin disorders.
引用
收藏
页码:490 / 494
页数:5
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