title: In vitro and in vivo inhibitory activity of the differentiation-inducing agent 9-(2-phosphonylmethoxyethyl)adenine (PMEA) against rat choriocarcinoma.
abstract: The acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA) has previously been shown to be a strong inducer of differentiation in several tumor cell lines. We have now investigated the in vitro differentiation-inducing and the in vivo antitumor, properties of PMEA in a rat choriocarcinoma tumor cell model. PMEA at 2 to 50 microM induced choriocarcinoma RCHO cell differentiation in vitro in a concentration-dependent manner, as monitored by morphological changes, induction of alkaline phosphatase and production and secretion of progesterone. Likewise, a clear dose-response relationship was established for the in vivo antitumor activity of PMEA in choriocarcinoma-bearing rats. (R)-PMPA, a structural analogue of PMEA which is much less effective than PMEA in inducing differentiation in vitro did not demonstrate any in vivo antitumor activity. This observation points to the specificity of the differentiation-inducing potential of PMEA.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Hatse
authors.forename: L
authors.initials: L
authors.lastname: Naesens
authors.forename: B
authors.initials: B
authors.lastname: Degrève
authors.forename: M
authors.initials: M
authors.lastname: Vandeputte
authors.forename: M
authors.initials: M
authors.lastname: Waer
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002822:Choriocarcinoma / Q000188:drug therapy* / Q000473:pathology; D008727:Methotrexate / Q000494:pharmacology; D063065:Organophosphonates; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D063065:Organophosphonates; D011374:Progesterone; C053001:adefovir; D000469:Alkaline Phosphatase; D000225:Adenine; D008727:Methotrexate