Inhibition of growth, production of insulin-like growth factor-II (IGF-II), and expression of IGF-II mRNA of human cancer cell lines by antagonistic analogs of growth hormone-releasing hormone in vitro.
Csernus. V J VJ; Schally. A V AV; Kiaris. H H; Armatis. P P
Key Findings
- GHRH antagonists (MZ-4-71 and MZ-5-156) significantly reduced proliferation of breast, prostate, and pancreatic cancer cells in vitro.
- These antagonists lowered both IGF‑II mRNA levels inside the cells and the amount of IGF‑II secreted into the culture medium.
- The inhibitory effect was weaker but still present in lung and ovarian cancer cells that produce large amounts of IGF‑II.
Practical Outcomes
- For self‑experimenters using sermorelin (a GHRH agonist) to boost growth hormone, this research hints that stimulating the GHRH pathway could increase IGF‑II production in some tissues, which might have implications for tumor growth. While the study does not provide a direct dosing protocol, it suggests monitoring IGF‑II–related markers if you are concerned about cancer risk. The findings are more relevant for understanding potential risks than for creating new performance‑enhancing regimens.
Summary
The study shows that chemicals that block the hormone that normally tells the pituitary to release growth hormone (called GHRH antagonists) can slow the growth of several cancer cell lines by cutting down the amount of a growth factor called IGF‑II that many tumors make themselves. This effect is separate from the usual growth‑hormone/IGF‑I pathway and works by interfering with the tumor’s own IGF‑II signaling loop.
Abstract
Antagonistic analogs of growth hormone-releasing hormone (GHRH) suppress growth of various tumors in vivo. This effect is exerted in part through inhibition of the GHRH-GH-insulin-like growth factor (IGF)-I axis. Nevertheless, because autocrine/paracrine control of proliferation by IGF-II also is a major factor in many tumors, the interference with this growth-stimulating pathway would offer another approach to tumor control. We thus investigated whether GHRH antagonists MZ-4-71 and MZ-5-156 also act on the tumor cells directly by blocking the production of IGF-II. An increase in the IGF-II concentration in the media during culture was found in 13 of 26 human cancer cell lines tested. Reverse transcription-PCR studies on 8 of these cell lines showed that they also expressed IGF-II mRNA. Antagonists of GHRH significantly inhibited the rate of proliferation of mammary (MDA-MB-468 and ZR-75-1), prostatic (PC-3 and DU-145), and pancreatic (MiaPaCa-2, SW-1990, and Capan-2) cancer cell lines as shown by colorimetric and [3H]thymidine incorporation tests and reduced the expression of IGF-II mRNA in the cells and the concentration of IGF-II secreted into the culture medium. Growth and IGF-II production of lung (H-23 and H-69) and ovarian (OV-1063) cancer cells that express mRNA for IGF-II and excrete large quantities of IGF-II also was marginally suppressed by the antagonists. These findings suggest that antagonistic analogs of GHRH can inhibit growth of certain tumors not only by inhibiting the GHRH-GH-IGF-I axis, but also by reducing the IGF-II production and by interfering with the autocrine regulatory pathway.
Study Information
pubmed
1999
1999-03-16T00:00:00.000Z
10.1073/pnas.96.6.3098