Luteinizing hormone releasing hormone-RNase A conjugates specifically inhibit the proliferation of LHRH-receptor-positive human prostate and breast tumor cells.
Human prostate and breast tumor cells produce luteinizing hormone-releasing hormone (LHRH) receptors on their cell surface even when they have lost dependency on sex steroid hormones for growth. To investigate whether LHRH can be used as a cell-binding moiety to deliver toxin molecules into prostate and breast tumor cells, LHRH-bovine RNase A conjugates were constructed using the chemical cross-linking method. The treatment of the LHRH receptor-positive cells such as prostate LNCapFGC and breast MCF7 tumor cells with LHRH-RNase A conjugates resulted in a dose-dependent inhibition of growth. The cytotoxic activities of these conjugates were effectively reduced by the presence of exogenous LHRH. Either free RNase A or LHRH alone did not affect the proliferation of these cells. The LHRH-RNase A conjugates did not show cytotoxicity against FRTL5 and TM4 cells which do not express the LHRH receptors. These results suggest that LHRH can be used as a cell-binding molecule for the specific delivery of toxin molecules into the cells which express LHRH receptors on their surface. Thus, a new class of biomedicines that act as fusion proteins between LHRH and toxins will give us a new avenue for the treatment of human prostate and breast cancers, regardless of their steroid hormone dependency.
Gho
Y S
YS
Department of Life Science, Pohang University of Science and Technology, Korea.
Chae
C B
CB
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007987:Gonadotropin-Releasing Hormone / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011966:Receptors, LHRH / Q000276:immunology / Q000627:therapeutic use; D012259:Ribonuclease, Pancreatic / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D000922:Immunotoxins; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D012259:Ribonuclease, Pancreatic