Abstract
Analogs of GnRH used for the treatment of sex steroid-independent tumors are not optimal because of endocrine side-effects. Lamprey gonadotropin- releasing hormone III (lGnRH-III), however, directly inhibits the growth of several tumor cell lines derived from reproductive organs. In this study, the signaling and antiproliferative effects of lGnRH-III on two breast, a colonic and a pancreatic cancer cell lines were investigated. Binding affinity of the peptide was determined by competitive receptor binding assays. Cell proliferation was measured following treatment for 3 days with lGnRH-III. Intracellular cAMP levels in response to lGnRH-III binding were quantified and effects of pertussis toxin (PTX), an inhibitor of Gi activation, on suppression of growth by lGnRH-III were examined. lGnRH-III had comparable affinities for receptors on all four cell lines and inhibited their growth at micromolar concentrations in a dose-dependent manner. PTX-sensitive decrease in cAMP levels in response to lGnRH-III in colonic and pancreatic cells was observed, while lGnRH-III increased intracellular [Ca2+] in both breast cancer cell lines. This study further indicates that the same receptors utilize different signal transduction pathways in different cancer cells.
Original language | English (US) |
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Pages (from-to) | 359-364 |
Number of pages | 6 |
Journal | International Journal of Peptide Research and Therapeutics |
Volume | 12 |
Issue number | 4 |
DOIs | |
State | Published - Dec 1 2006 |
All Science Journal Classification (ASJC) codes
- Analytical Chemistry
- Bioengineering
- Biochemistry
- Molecular Medicine
- Drug Discovery