In vitro activity of human chorionic gonadotropin (hCG)--doxorubicin conjugates against ovarian cancer cells.
BACKGROUND
Despite radical surgery and the introduction of novel chemotherapeutic agents, the prognosis of ovarian cancer remains poor. Since in the past the potential role of gonadotropins in the induction and progression of ovarian cancer has been discussed, we conjugated doxorubicin to human chorionic gonadotropin (hCG) in order to specifically target ovarian cancer cells.


METHODS
Doxorubicin was conjugated to hCG via glutaraldehyde. 48 hours post seeding, NIH:OVCAR 3 cells were treated with various concentrations of hCG-conjugated and non-conjugated doxorubicin for 2 hours. Cells were cultured for a total of 168 hours. Cell growth was monitored by a crystal violet assay.


RESULTS
Conjugating doxorubicin to hCG resulted in an average specific uptake of 22 mol doxorubicin per mol protein (range 3.0-43.3 mol). Incubating NIH:OVCAR 3 cells for 2 hours with the conjugate led to a more than 8 fold increase of the IC50 values compared to non-conjugated doxorubicin (0.55 microM versus 4.43 microM). The antiproliferative activity of both conjugated and free doxorubicin was detectable up to 168 hours post treatment.


CONCLUSIONS
The present experiments clearly demonstrate a more than 8-fold increase in cytotoxicity of the conjugates compared to free doxorubicin. It was also shown that this effect was not restricted to an acute toxic event but that it resulted in a prolonged antiproliferative activity.
Beck
E P
EP
Staedtische Frauenklinik Stuttgart, Germany.
Vincenti
D
D
Licht
P
P
Berkholz
A
A
Jäger
W
W
Lang
N
N
Merkle
E
E
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006063:Chorionic Gonadotropin; D004317:Doxorubicin