Linker-based GnRH-PE chimeric proteins inhibit cancer growth in nude mice.
Since the number of cancer-related deaths has not decreased in recent years, major efforts are being made to find new drugs for cancer treatment. In this report we introduce the gonadotropin releasing hormone-Pseudomonas exotoxin (GnRH-PE) based chimeric proteins L-GnRH-PE66 and L-GnRH-PE40. These proteins are composed of a GnRH moiety attached to modified forms of Pseudomonas exotoxin via a polylinker (gly4ser)2. The chimeric proteins L-GnRH-PE66 and L-GnRH-PE40 have the ability to target and kill adenocarcinoma cell lines in vitro, whereas non-adenocarcinoma cell lines are not affected. We demonstrate that L-GnRH-PE66 and L-GnRH-PE40 efficiently inhibit cancer growth. Nude mice were injected subcutaneously with the SW-48 adenocarcinoma cell line to produce xenograft tumours. When the tumours were established and visible, the animals were injected with chimeric proteins for 10 days. At the end of this period, a reduction of up to 3-fold in tumor size was obtained in the treated mice, as compared with the control group, which received equivalent amounts of GnRH; the difference was even greater 13 days after termination of treatment. Thus, the chimeric proteins L-GnRH-PE66 and L-GnRH-PE40 are promising candidates for treatment of a variety of adenocarcinomas and their use in humans should be considered.
Ben-Yehudah
A
A
Department of Cellular Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Yarkoni
S
S
Nechushtan
A
A
Belostotsky
R
R
Lorberboum-Galski
H
H
D036002:ADP Ribose Transferases; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy*; D005069:Evaluation Studies as Topic; D005098:Exotoxins / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D005098:Exotoxins; C120463:L-GnRH-PE40; C120462:L-GnRH-PE66 protein, chimeric; D011993:Recombinant Fusion Proteins; D007987:Gonadotropin-Releasing Hormone; D036002:ADP Ribose Transferases