Cytotoxic effect of conjugates of doxorubicin and human chorionic gonadotropin (hCG) in breast cancer cells.
Cytotoxic activity of drug conjugates of human chorionic gonadotropin (hCG) and doxorubicin alone was investigated compared to doxorubicin in breast cancer cells with and without expression of hCG receptors. Expression of hCG receptor was determined in MCF-7 and MB231 breast cancer cell line using a multiplex nested rt-PCR approach. The entire sequence of mRNA encoding for hCG receptor was detected in MCF-7 but not in MB231 breast cancer cell line. Cytostatic effect of doxorubicin-hCG conjugates was investigated in these cell lines in comparison to unconjugated doxorubicin. The number of viable cells was determined after 24, 48, 72, 96, and 120h. To exclude non-specific uptake of the carrier hCG from the culture media, a similar experiment was performed with albumin-doxorubicin conjugates. The number of viable cells decreased in a concentration depending manner after doxorubicin and hCG-doxorubicin conjugate treatment. However, the cytotoxic effect of hCG-doxorubicin conjugate was 10-fold increased compared to unconjugated doxorubin in hCG-receptor positive MCF-7 but not in hCG-receptor negative MB231 cells. Albumin-doxorubicin conjugates showed no increased toxicity compared to doxorubicin. We conclude that the cytotoxic effect of hCG-doxorubicin conjugates is mediated specifically via the hCG receptor. By using hCG conjugates, the development of more selective cytostatics can be achieved.
Gebauer
Gerhard
G
Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany. ggebauer@i-mednet.org
Fehm
Tanja
T
Beck
Eberhard P
EP
Berkholz
Alexander
A
Licht
Peter
P
Jäger
Wolfram
W
D000418:Albumins; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D012333:RNA, Messenger / Q000032:analysis; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000418:Albumins; D000903:Antibiotics, Antineoplastic; D006063:Chorionic Gonadotropin; D004337:Drug Carriers; D008024:Ligands; D012333:RNA, Messenger; D011974:Receptors, LH; D004317:Doxorubicin