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 antitu-mor properties of PMEA in a rat choriocarcinoma tumor cell model. PMEA at 2 to 50 μM 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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
De Clercq, E., Holy, A., Rosenberg, I., Sakuma, T., Balzarini, J., and Maudgal, P.C. Nature 323: 464–467 (1986).
De Clercq, E., Sakuma, T., Baba, M., Pauwels, R., Balzarini, J., Rosenberg, I. and Holy, A. Antiviral Res. 8: 261–272 (1987).
Heijtink, R.A., De Wilde, G.A., Kruining, J., Berk, L., Balzarini, J., De Clercq, E., Holy, A., and Schalm, S.W. Antiviral Res. 21: 141–153 (1993).
Balzarini, J., Naesens, L., Herdewijn, P., Rosenberg, I., Holy, A., Pauwels, R., Baba, M., Johns, D.G. and De Clercq, E. Proc. Natl. Acad. Sci. USA, 86: 332–336 (1989).
Balzarini, J., Naesens, L., and De Clercq, E. Int. J. Cancer 46: 337–340 (1990).
Balzarini, J., Verstuyf, A., Hatse, S., Goebels, J., Sobis, H., Vandeputte, M., and De Clercq, E. Int. J. Cancer 61: 130–137 (1995).
Verstuyf, A., Sobis, H., Goebels, J., Fonteyn, E., Cassiman, J.J., and Vandeputte, M. Int. J. Cancer 45: 752–756 (1990).
Verstuyf, A., Sobis, H., and Vandeputte, M. Int. J. Cancer 44: 879–884 (1989).
Friedman, S.J., and Skehan, P. Cancer Res. 39: 1960–1967 (1979).
Botte, V, Tramontana, S., and Chieffi, G. J. Endocrinol. 40: 189–194 (1968).
Campbell, W.J., Larsen, D., Deb, S., Kwok, S.C.M., and Soares, M.J. Placenta 12: 227–237 (1991).
Holy, A., and Rosenberg, I. Collect. Czech. Chem. Commun. 52: 2801–2809 (1987).
Balzarini, J., Hao, Z., Herdewijn, P., Johns, D.G., and De Clercq, E. Proc. Natl. Acad. Sci. USA 88: 1499–1503 (1991).
Balzarini, J., Holy, A., **drich, J., Naesens, L., Snoeck, R., Schols, D. and De Clercq, E. Antimicrob. Agents Chemother. 37: 332–338 (1993).
Verstuyf, A., Goebels, J., Sobis, H., and Vandeputte, M. Tumor Biol. 14: 46–54 (1993).
Pommier, Y., and Lokiec, F. Chimiothé rapie anticancereuse 31: 3083–3089 (1981).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media New York
About this chapter
Cite this chapter
Hatse, S. et al. (1998). In Vitro and in Vivo Inhibitory Activity of the Differentiation-Inducing Agent 9-(2-Phosphonylmethoxyethyl)Adenine (Pmea) Against Rat Choriocarcinoma. In: Griesmacher, A., Müller, M.M., Chiba, P. (eds) Purine and Pyrimidine Metabolism in Man IX. Advances in Experimental Medicine and Biology, vol 431. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5381-6_117
Download citation
DOI: https://doi.org/10.1007/978-1-4615-5381-6_117
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7456-5
Online ISBN: 978-1-4615-5381-6
eBook Packages: Springer Book Archive