HEXADECYLPHOSPHOCHOLINE DIFFERS FROM CONVENTIONAL CYTOSTATIC AGENTS

Alkylphosphocholines, and especially their main representative hexadec ylphosphocholine (HPC), show high anticancer activity in methylnitroso urea(MNU)-induced autochthonous rat mammary carcinoma. The regression of MNU-induced rat mammary carcinoma during HPC treatment can be evalu ated by computed tomography and sonography. This allows a noninvasive monitoring of therapy in vivo (tumor size, morphology, and blood suppl y). Both diagnostic modalities can show a rapid concentric decrease in tumor volume as well as the appearance of cystic, scarry, and necroti c areas in the tumor tissue as a result of HPC treatment. In addition, prior to, during and after therapy tumor perfusion can be assessed by color Doppler sonography in vivo. A more than 4-fold difference in HP C efficacy was observed when the colony growth of explanted MNU-induce d mammary carcinoma cells was measured in the methylcellulose colony a ssay (IC50 = 180 mumol HPC/l) and the Hamburger Salmon colony assay (I C50 = 740 mumol HPC/l). In the latter assay, growth of concomitantly s eeded untransformed cells, especially of fibroblasts, is much lower th an in the methylcellulose colony assay. We therefore assume that the a ntitumor efficacy of HPC against MNU-induced mammary carcinoma is enha nced by neighboring cells such as fibroblasts. Cell culture experiment s with the three MNU-induced rat mammary carcinoma cell clones 1-C-2, 1-C-30, and 1-C-32 revealed IC50 values in the range of 50-70 mumol HP C/l. The volume of 1-C-2 cells increased up to 4-fold after 72 h of pe rmanent exposure to 100 mumol HPC/l, a concentration that completely i nhibited proliferation of tumor cell numbers without being cytotoxic. Nucleotide triphosphate levels dropped significantly after 24 h and we re slowly restored in spite of continued exposure. After 72 h, they ne arly reached those levels observed in plateau-phase cells. This sugges ts that HPC-induced growth inhibition has similarities with physiologi cally occurring growth arrest. Finally, replication of RNA viruses and DNA viruses was suppressed 30-fold and 7-fold, respectively, at low c oncentrations of HPC (12 mumol/l), which caused no or negligible growt h inhibition in the virus-harboring cells, thus demonstrating specific anti-viral activity of HPC. From these observations we conclude that HPC differs in many important aspects from conventional cytostatic age nts and is certainly worth following-up in further investigations.