Antiproliferative effects of octadecyloxyethyl 9-[2-(phosphonomethoxy)ethyl]guanine against Me-180 human cervical cancer cells in vitro and in vivo.

Background/Aims: 9-[2-(phosphonomethoxy) ethyl] guanine (PMEG) is one of the most active antiproliferative compounds in a series of acyclic nucleoside phosphonates and is active in intraperitoneal P388 tumors in mice. Methods: We synthesized octadecyloxyethyl (ODE) and hexadecyloxypropyl esters of PMEG and compared their antiproliferative activity with unmodified PMEG in primary human fibroblasts and CaSki, Me-180 and HeLa human cervical cancer cell lines in vitro. Results: ODE-PMEG had excellent antiproliferative activity in vitro in this panel of human cervical cancers. We compared the effects of ODE-PMEG and ODE-cidofovir (ODE-CDV) in a solid tumor model using Me-180 human cervical cancer cell lines in athymic nude mice. Intratumoral injection of 25 mu g of ODE-PMEG or 100 mu g of ODE-CDV daily for 21 days followed by observation for 20-35 days resulted in near-complete disappearance of measurable cervical cancers. Conclusion: ODE-PMEG may be suitable for local or topical treatment of cervical dysplasia. Copyright (C) 2010 S. Karger AG, Basel