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Differential effects of LHRH and somatostatin analogs on human breast cancer
S T Brower1, A V Schally, T W Redding
1Department of Surgery, Mount Sinai Medical Center, New York, New York 10029.
Abstract:
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)
Insights
Luteinizing hormone-releasing hormone (LHRH) and somatostatin analogs impact human breast cancer cell growth. Combinations of LHRH agonists and antagonists significantly inhibited tumor cell DNA synthesis, with varying effects in the presence of estradiol.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Luteinizing hormone-releasing hormone (LHRH) and somatostatin (SS) are peptide hormones with known roles in endocrine regulation.
- Their direct effects on human mammary tumor cell growth warrant investigation for potential therapeutic strategies.
Purpose of the Study:
- To analyze the effects of novel LHRH and SS analogs on DNA synthesis in MCF-7 human breast cancer cells.
- To determine the impact of these analogs, individually and in combination, on cancer cell proliferation.
Main Methods:
- MCF-7 breast cancer cells were cultured and treated with various concentrations of LHRH agonists (D-Trp6-LHRH, zoladex), LHRH antagonists (SB30, SB75), and an SS analog (RC 160).
- DNA synthesis was measured by 3[H]thymidine incorporation at 48, 72, and 96 hours.
- Experiments were conducted with and without the addition of estradiol.
Main Results:
- The LHRH agonist D-Trp6-LHRH and antagonist SB30, when combined, significantly inhibited DNA synthesis by 50% at 48 hours.
- D-Trp6-LHRH showed dose-dependent inhibition of DNA synthesis at 72 and 96 hours in the absence of estradiol.
- SB30 demonstrated significant stimulation of DNA synthesis, particularly at higher concentrations and in the presence of estradiol, reversing D-Trp6-LHRH's inhibitory effect.
Conclusions:
- Specific LHRH and SS analogs exhibit direct effects on human breast cancer cell proliferation.
- Combinations of LHRH agonists and antagonists may offer a strategy for inhibiting tumor growth.
- The presence of estradiol can modulate the response of breast cancer cells to these peptide hormone analogs.