Antiproliferative effects of octadecyloxyethyl 9-[2-(phosphonomethoxy)ethyl]guanine against Me-180 human cervical cancer cells in vitro and in vivo.
OBJECTIVE
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 microg of ODE-PMEG or 100 microg of ODE-CDV daily for 21 days followed by observation for 20-35 days resulted in near-complete disappearance of measurable cervical cancers.


CONCLUSIONS
ODE-PMEG may be suitable for local or topical treatment of cervical dysplasia.
Valiaeva
Nadejda
N
Department of Medicine, University of California, San Diego, La Jolla, Calif., and Veterans Medical Research Foundation, San Diego, CA 92093-0676, USA.
Trahan
Julissa
J
Aldern
Kathy A
KA
Beadle
James R
JR
Hostetler
Karl Y
KY
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D063065:Organophosphonates / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D009943:Organophosphorus Compounds / Q000627:therapeutic use* / Q000633:toxicity; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C550608:octadecyloxyethyl 9-(2-(phosphonomethoxy)ethyl)guanine; C063380:9-((2-phosphonylmethoxy)ethyl)guanine; D006147:Guanine; D000225:Adenine