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Gonadotropin-releasing hormone type II antagonists induce apoptotic cell death in human endometrial and ovarian cancer cells in vitro and in vivo.
- Source :
-
Cancer research [Cancer Res] 2007 Feb 15; Vol. 67 (4), pp. 1750-6. - Publication Year :
- 2007
-
Abstract
- In human endometrial and ovarian cancers, gonadotropin-releasing hormone type I (GnRH-I), GnRH-II, and their receptors are parts of a negative autocrine regulatory system of cell proliferation. Based on a tumor-specific signal transduction, GnRH-I and GnRH-II agonists inhibit the mitogenic signal transduction of growth factor receptors and related oncogene products associated with tyrosine kinase activity via activation of a phosphotyrosine phosphatase resulting in down-regulation of cancer cell proliferation. Induction of apoptosis is not involved. In this study, we show that treatment of human endometrial and ovarian cancer cells with GnRH-II antagonists results in apoptotic cell death via dose-dependent activation of caspase-3. The antitumor effects of the GnRH-II antagonists could be confirmed in nude mice. GnRH-II antagonists inhibited the growth of xenotransplants of human endometrial and ovarian cancers in nude mice significantly, without any apparent side effects. Thus, GnRH-II antagonists seem to be suitable drugs for an efficacious and less toxic endocrine therapy for endometrial and ovarian cancers.
- Subjects :
- Animals
Caspase 3 metabolism
Cell Growth Processes drug effects
Cell Line, Tumor
Dose-Response Relationship, Drug
Drug Interactions
Endometrial Neoplasms metabolism
Endometrial Neoplasms pathology
Enzyme Activation drug effects
Female
Gonadotropin-Releasing Hormone antagonists & inhibitors
Gonadotropin-Releasing Hormone pharmacology
Humans
Membrane Potential, Mitochondrial drug effects
Mice
Mice, Nude
Ovarian Neoplasms metabolism
Ovarian Neoplasms pathology
Pertussis Toxin pharmacology
Receptors, LHRH metabolism
Xenograft Model Antitumor Assays
Apoptosis drug effects
Endometrial Neoplasms drug therapy
Gonadotropin-Releasing Hormone analogs & derivatives
Ovarian Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 67
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 17308117
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-06-3222