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.