title: In vitro and in vivo antitumoral activity of alkylphosphonates.
abstract: Hexadecylphosphocholine is a new antitumour agent with a highly selective activity in chemically induced mammary tumours. It was suggested, that hexadecylphosphocholine is a pro-drug, cleavable by phospholipases C and/or D, creating hexadecanol or hexadecylphosphate as the active principle. To test this hypothesis, the antineoplastic activity of three alkylphosphonates, cleavable either by phospholipase C or D, are compared with those of the parent compound, hexadecylphosphocholine. Cell culture experiments, in which radiolabelled alkylphosphonates were incubated with a neoplastic cell line, showed no metabolism even after 3 days of incubation. In in vivo experiments with dimethylbenzanthracene-induced rat mammary carcinomas, all three alkylphosphonates showed antineoplastic activity, although none of them reached the high activity of hexadecylphosphocholine. These results indicate that the antitumoral activity of alkylphosphocholines and alkyl lysophosphatidylcholines is due to direct toxicity and not dependent on metabolism by phospholipases C or D or related enzymes.
authors.affiliation: Department of Chemical Research, Dr. Karl Thomae GmbH, Biberach/Riss, F.R.G.
authors.forename: U J
authors.initials: UJ
authors.lastname: Ries
authors.forename: E A
authors.initials: EA
authors.lastname: Fleer
authors.forename: A
authors.initials: A
authors.lastname: Breiser
authors.forename: C
authors.initials: C
authors.lastname: Unger
authors.forename: J
authors.initials: J
authors.lastname: Stekar
authors.forename: K
authors.initials: K
authors.lastname: Fenneberg
authors.forename: H
authors.initials: H
authors.lastname: Eibl
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008938:Mitosis / Q000187:drug effects; D010739:Phospholipase D / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011355:Prodrugs; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D010767:Phosphorylcholine; C039128:miltefosine; D010738:Type C Phospholipases; D010739:Phospholipase D