Direct growth inhibition of human endometrial cancer cells by the gonadotropin-releasing hormone antagonist SB-75: role of apoptosis.
OBJECTIVE
Our objective was to study the direct action of the gonadotropin-releasing hormone antagonist SB-75 and the agonist buserelin on the proliferation of endometrial cancer cells.


METHODS
Two human endometrial cell lines that differ in histologic subtype and estrogen receptor content were treated with gonadotropin-releasing hormone analog. We measured the number of viable cells, cell cycle parameters, and apoptotic processes.


RESULTS
Growth of the Ishikawa cells was inhibited by SB-75 in a dose-dependent manner. 17 beta-Estradiol partially abolished the inhibitory effect of SB-75. The growth of the HEC-1A cells was not affected by the antagonist. Neither endometrial cancer cell line showed significant sensitivity to the agonist buserelin. Tenfold concentration of the gonadotropin-releasing hormone agonist did not abolish the inhibitory effect of the antagonist on cell growth. The growth inhibition was not associated with any change in cell cycle parameters but was associated with an induction of apoptosis.


CONCLUSIONS
The gonadotropin-releasing hormone antagonist SB-75 directly inhibits the growth of some human endometrial cancer cells and thus may be suitable for the treatment of endometrial tumors.
Kleinman
D
D
Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Soroka Medical Center of Kupat Holim, Beer-Sheva, Israel.
Douvdevani
A
A
Schally
A V
AV
Levy
J
J
Sharoni
Y
Y
D000231:Adenocarcinoma, Papillary / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002064:Buserelin / Q000494:pharmacology / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D016889:Endometrial Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D011960:Receptors, Estrogen / Q000032:analysis; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D011960:Receptors, Estrogen; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; C062876:cetrorelix; D002064:Buserelin