The effect of hexadecylphosphocholine on the proliferation of human keratinocytes in vitro and in vivo

Phospholipid analogs represent a new class of antiproliferative drugs. The first analog to be introduced into clinical studies was the alkylphosphocho line, hexadecylphosphocholine (HPC), which is successfully used for the top ical treatment of skin metastases of mammary carcinomas. In order to invest igate other possible therapeutic approaches for psoriasis, basal cell carci nomas or squamous cell carcinomas, the effect of hexadecylphosphocholine on the proliferation of human keratinocytes and different keratinocyte-derive d cell lines in vitro was examined. It was shown that HPC is a potent inhib itor of normal human keratinocytes, ras-transfected HaCaT cells and the squ amous cell carcinoma cell line SCL-1. However, in the first clinical trial for treating psoriasis patients topically with HPC only a marginal benefici al effect was seen, which may be explained by an insufficient penetration a nd uptake of the lipid analog. Furthermore, evidence is provided that the a ntiproliferative effect of HPC is mediated by an increase of the proapoptot ic lipid ceramide, resulting from the HPC-induced inhibition of phosphatidy lcholine/sphingomyelin biosynthesis. (C) Prous Science. All right reserved.