Lipophilization of somatostatin analog RC‐160 with long chain fatty acid improves its antiproliferative and antiangiogenic activity in vitro
Open Access
- 30 January 2000
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 129 (1) , 101-109
- https://doi.org/10.1038/sj.bjp.0702990
Abstract
The therapeutic potential of the somatostatin analogue RC‐160 having antiproliferative activity, is limited by its short serum half life. To overcome this limitation, fatty acids namely butanoic acid and myristic acid were conjugated to the N‐terminal residue of RC‐160. The lipophilized derivatives of RC‐160 were synthesized, purified by reverse phase HPLC and characterized by ES‐mass spectroscopy. The antiproliferative activity of lipophilized derivatives of RC‐160 on the growth of MIA‐PaCa2 (human pancreatic carcinoma), DU145 (human prostate carcinoma), ECV304 (human umbilical chord endothelioma), as well as their antiangiogenic activity was evaluated in vitro. The relative stability of myristoyl‐RC‐160 towards degradation by proteases and serum was also determined. Myristoyl‐RC‐160 exhibited significantly higher antiproliferative efficacy than RC‐160, on the above cell lines (PPPin vitro (PBritish Journal of Pharmacology (2000) 129, 101–109; doi:10.1038/sj.bjp.0702990Keywords
This publication has 31 references indexed in Scilit:
- (Stearyl, Norleucine17) VIP hybrid antagonizes VIP receptors on non-small cell lung cancer cellsLife Sciences, 1997
- A somatostatin analogue inhibits MAP kinase activation and cell proliferation in human neuroblastoma and in human small cell lung carcinoma cell linesFEBS Letters, 1996
- Functional Characterization of the Spontaneously Transformed Human Umbilical Vein Endothelial Cell Line ECV304: Use in anin VitroModel of AngiogenesisExperimental Cell Research, 1996
- Synthesis of Potent Cyclic Hexapeptide NK-1 Antagonists. Use of a Minilibrary in Transforming a Peptidal Somatostatin Receptor Ligand into an NK-1 Receptor Ligand via a Polyvalent PeptidomimeticJournal of Medicinal Chemistry, 1996
- Somatostatin analog RC‐160 inhibits growth of CFPAC‐1 human pancreatic cancer cells in vitro and intracellular production of cyclic adenosine monophosphateInternational Journal of Cancer, 1995
- Molecular biology of somatostatin receptorsTrends in Neurosciences, 1993
- Somatostatin Analogue RC-160 and LH-RH Antagonist SB-75 Inhibit Growth of MIA PaCa-2 Human Pancreatic Cancer Xenografts in Nude MicePancreas, 1993
- Solid phase peptide synthesis utilizing 9‐fluorenylmethoxycarbonyl amino acidsInternational Journal of Peptide and Protein Research, 1990
- Implications of the X-ray structure of deamino-oxytocin to agonist/antagonist-receptor interactionsTrends in Pharmacological Sciences, 1987
- Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reactionBiochemical Pharmacology, 1973