LHRH receptor targeted therapy for breast cancer.
Breast cancer remains the most common cancer among women, with an estimated 212,920 new cases and 40,970 deaths in the United States in 2006. The present work extends the studies of nanoparticles targeted to the luteinizing hormone-releasing hormone (LHRH) receptor which is overexpressed in breast, ovarian, endometrial and prostate cancer cells. In contrast, LHRH receptors are not expressed, or expressed at a low level in most visceral organs. In our studies, we conjugated Fe3O4 nanoparticles (20-30 nm) with [D-Trp6]LHRH (Triptorelin), a decapeptide analog of LHRH currently used for treatment of sex-hormone-dependent tumors. Conjugation of [D-Trp6]LHRH to Fe3O4 particles retained its binding affinity and biological activity for the LHRH receptor. Treatment of two separate breast tumor cell lines (MCF-7 and MDA-MB231) with these conjugated nanoparticles resulted in 95-98% cell death and loss of viability within 24 h whereas no change in cell proliferation or cell apoptosis was observed in cells treated with equal amounts of either [D-Trp6]LHRH or unconjugated Fe3O4 nanoparticles. These studies provide critical and important information regarding use of LHRH receptor targeted therapy for breast cancer.
Kakar
S S
SS
Department of Medicine and James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Jin
H
H
Hong
B
B
Eaton
J W
JW
Kang
Kyung A
KA
D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053768:Metal Nanoparticles / Q000627:therapeutic use*; D008956:Models, Chemical; D011966:Receptors, LHRH / Q000378:metabolism*; D017329:Triptorelin Pamoate / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D005290:Ferric Compounds; D011966:Receptors, LHRH; D017329:Triptorelin Pamoate; C000499:ferric oxide