In vitro investigations on the antineoplastic effect of hexadecylphosphocholine.
The in vitro antineoplastic activity of hexadecylphosphocholine (HPC, CAS 58066-85-6) on methylnitrosourea (MNU)-induced mammary carcinoma in Sprague-Dawley rats and human mammary carcinoma was investigated with the modified Hamburger-Salmon-Colony-Assay (HSCA). The effect of HPC was also compared with ilmofosine (alkyllysophospholipid derivative) and N-(2-chloroethyl-N-nitroso-N'-2-hydroxyethylurea (HECNU). Moreover, the modified HSCA was performed with bone marrow cells and KB cells. In this investigation, no specific antineoplastic effect of the test compounds on MNU-induced mammary carcinoma and human mammary carcinoma was found in HSCA. Thus the antineoplastic activity of the compounds could not be compared on these cell types. In vitro, effects were only observed in bone marrow and KB cells at a very low concentration. The in vitro effect of HPC on mammary carcinoma cells, evaluated through HSCA, did not predict the effect of HPC in vivo. The reason has remained unknown but some hypotheses are discussed. Because of the contrary results of HPC in vitro and in vivo, it should be pointed out that drug development in this class of compounds mainly has to depend on in vivo experiments.
Deutsches Krebsforschungszentrum, Institut für Toxikologie und Chemotherapie, Heidelberg, Fed. Rep. of Germany.
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Yanapirut
M R
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Berger
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M
Reinhardt
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D
Schmähl
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells; D001943:Breast Neoplasms / Q000473:pathology; D003114:Colony-Forming Units Assay; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D008770:Methylnitrosourea; D009368:Neoplasm Transplantation; D009607:Nitrosourea Compounds / Q000494:pharmacology; D010742:Phospholipid Ethers / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D010742:Phospholipid Ethers; D010767:Phosphorylcholine; C039128:miltefosine; C043297:ilmofosine; D008770:Methylnitrosourea; C013876:elmustine