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 |
|---|---|
| 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 2006 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
Cite this
Different signal responses to lamprey GnRH-III in human cancer cells. / Herédi-Szabó, Krisztina; Murphy, Richard F.; Lovas, Sándor.
In: International Journal of Peptide Research and Therapeutics, Vol. 12, No. 4, 12.2006, p. 359-364.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Different signal responses to lamprey GnRH-III in human cancer cells
AU - Herédi-Szabó, Krisztina
AU - Murphy, Richard F.
AU - Lovas, Sándor
PY - 2006/12
Y1 - 2006/12
N2 - 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.
AB - 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.
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U2 - 10.1007/s10989-006-9039-y
DO - 10.1007/s10989-006-9039-y
M3 - Article
VL - 12
SP - 359
EP - 364
JO - International Journal of Peptide Research and Therapeutics
JF - International Journal of Peptide Research and Therapeutics
SN - 1573-3149
IS - 4
ER -