Differential effects of LHRH and somatostatin analogs on human breast cancer.
We have been interested in the possible direct effects of luteinizing hormone releasing hormone (LHRH) and somatostatin (SS) analogs on the growth of human mammary tumor cells. Four recently synthesized peptide hormones including the LHRH agonists D-Trp6-LHRH and zoladex, LHRH antagonists SB30 and SB75, and the somatostatin analog RC 160 were analyzed for their effects on DNA synthesis of MCF-7 breast cancer cells in culture. At 48 hr, D-Trp6-LHRH and SB30 did not show significant effects (dose range, 10(-12)-10(-6) M). However, the combination of these two peptides at 10(-10) M produced significant inhibition of 3[H]thymidine incorporation (50% control). At 72 hr in the absence of estradiol-stimulated growth, D-Trp6-LHRH showed inhibition at 10(-12) and 10(-10) M (P less than 0.005 and 0.001). At higher concentrations, no significant inhibition was noted. In contrast to D-Trp6, SB30 (antagonist) showed no inhibition but significant stimulation of DNA synthesis at 10(-6) and 10(-4) M. In the presence of added estradiol (10(-9) M), complete reversal of D-Trp6-LHRH analog inhibition is noted. In contrast, there is persistent stimulation by SB30 (P less than 0.001). At 96 hr, D-Trp6-LHRH continued to show maximal inhibition of 70% in the absence of estradiol. SB30 stimulated DNA synthesis 100% at 10(-6) M. At 72 hr, the SS analog RC 160 demonstrated significant inhibition (53%) that was similar to D-Trp6 and SB75 peptides.(ABSTRACT TRUNCATED AT 250 WORDS)
Brower
S T
ST
Department of Surgery, Mount Sinai Medical Center, New York, New York 10029.
Schally
A V
AV
Redding
T W
TW
Hollander
V P
VP
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002064:Buserelin / Q000031:analogs & derivatives / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D017273:Goserelin; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology*; D017329:Triptorelin Pamoate; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004967:Estrogens; D006728:Hormones; D017329:Triptorelin Pamoate; D017273:Goserelin; C065822:LHRH, N-Ac-Nal(1)-4-Cl-Phe(2)-Trp(3)-Cit(6)-AlaNH2(10)-; C051458:vapreotide; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; C062876:cetrorelix; D002064:Buserelin