A study found that a drug that blocks growth‑hormone‑releasing hormone (GH‑RH) can lower the activity of telomerase, an enzyme tumors need to keep growing, in brain‑cancer cells in mice and in cell cultures. This effect seems to come from turning down a gene called hTRT that makes part of telomerase, not from changes in other related genes.

Antagonists of growth hormone-releasing hormone (GH-RH) inhibit the growth of various tumors through mechanisms that involve the suppression of the insulin-like growth factor I and/or insulin-like growth factor II levels or secretion. In the present study, we tested the hypothesis that the tumor inhibition is associated with a decrease in telomerase activity because telomerase is considered obligatory for continued tumor growth. Nude mice bearing xenografts of U-87MG human glioblastomas were treated with GH-RH antagonist MZ-5-156. Telomerase activity was assessed by the telomerase repeat amplification protocol. Treatment with MZ-5-156 reduced levels of telomerase activity as compared with controls. When U-87 glioblastomas, H-69 small cell lung carcinomas, H-23 non-small cell lung carcinomas, and MDA-MB-468 breast carcinoma cells were cultured in vitro, addition of 3 microM MZ-5-156 also inhibited telomerase activity. Reverse transcription-PCR analysis revealed that in U-87MG glioblastomas, the expression of the hTRT gene encoding for the telomerase catalytic subunit was significantly decreased by MZ-5-156, whereas the levels of mRNA for hTR and TP1, which encode for the telomerase RNA and telomerase-associated protein, respectively, were unaffected. The repression of the telomerase activity was not accompanied by a significant decrease of mRNA level for the c-myc protooncogene that regulates telomerase. Our findings suggest that tumor inhibition induced by the GH-RH antagonists in U-87MG glioblastomas is associated with the down-regulation of the hTRT gene, resulting in a decrease in telomerase activity. Further studies are needed to establish whether GH-RH antagonists produce telomerase inhibition in other tumors.