Antiproliferative efficacy of the somatostatin analogue TT-232 in human melanoma cells and tumours.
BACKGROUND
TT-232, a somatostatin analogue, induces apoptosis in various tumours. The aim of our study was to characterise its effect on human melanoma cells and tumours.


METHODS
Proliferation of seven melanoma cell lines was tested in vitro with the methylene blue test. D10 and 205 cells were also implanted into CB17-scid mice which received 30-150-750 micrograms/kg/day of TT-232 or saline. Animals with 205 cells received twice-daily subcutaneous injections whereas animals with D10 cells were treated with osmotic mini-pumps. In addition, TT-232 metabolites were generated with tissue homogenates and tested in vitro.


RESULTS
TT-232 strongly inhibited proliferation of all cell lines in vitro and tumour growth in vivo. Two out of 8 animals (30-150 micrograms/kg) in the 205 model and one out of 8(150 micrograms/kg) in the D10 model became completely tumour-free at the 11th and 9th day of treatment, respectively. TT-232 was degraded only by liver homogenate whilst its metabolite had no antiproliferative effect in vitro.


CONCLUSIONS
TT-232 is a promising drug candidate for melanoma.
Schwab
R E
RE
3rd Department of Medicine MAV Hospital, Podmaniczky u. 111, H-1062 Budapest, Hungary. schwab@puskin.sote.hu
Froidevaux
S
S
Paku
S
S
Tejeda
M
M
Szende
B
B
Pap
A
A
Beglinger
C
C
Eberle
A N
AN
Kéri
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D010456:Peptides, Cyclic / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013004:Somatostatin / Q000031:analogs & derivatives*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C094462:TT2-32; D013004:Somatostatin