A synthetic peptide derived from the human eosinophil-derived neurotoxin induces apoptosis in Kaposi's sarcoma cells.
Several commercial preparations of human chorionic gonadotropin (hCG) have been tested as therapy for Kaposi's sarcoma (KS) in clinical trials, but with discordant outcomes. We also have found dramatic differences in the cytotoxic effects of four different commercial hCG preparations on an established KS cell line, KSIMM. A co-purified moiety (ies) present in these preparations may explain these differences. The eosinophil-derived neurotoxin ribonuclease, extended with four extra residues ((-4)EDN), has been suggested to be the putative anti-KS compound in the hCG preparations, being specifically recognized by the cells through its N terminal extension. We therefore synthesized a 16-residue peptide (MSLHV-NT12 EDN), made to resemble the active recognition sequence of (-4)EDN. MSLHV-NT12 EDN displays a dose-dependent cytotoxic effect on KSIMM (killing 50% of the cells at 9 microg/ml). The cytotoxic effect is specific for KS cells, MSLHV-NT12 EDN being harmless even at 100 microg/ml for a melanoma cell line (SK-MEL-28) or for normal human fibroblasts. We also demonstrated that MSLHV-NT12 EDN induces apoptosis in KSIMM cells. In conclusion, MSLHV-NT12 EDN is a specific proapoptotic substance for KS cells, which warrants further investigation into its in vivo effects.
Dricu
Anica
A
Department of Oncology Pathology, Cancer Centrum Karolinska, Karolinska Hospital, RS-00 17176, Stockholm, Sweden. anica.dricu@onkpat.ki.se
Sergiu-Bogdan
Catrina
C
Brismar
Kerstin
K
Biberfeld
Peter
P
Andersson
Leif C
LC
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D006063:Chorionic Gonadotropin / Q000737:chemistry / Q000494:pharmacology / Q000652:urine; D047208:Eosinophil-Derived Neurotoxin; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D012260:Ribonucleases / Q000737:chemistry / Q000494:pharmacology*; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000473:pathology
D006063:Chorionic Gonadotropin; D009842:Oligopeptides; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases