Antagonist of growth hormone-releasing hormone MIA-690 attenuates the progression and inhibits growth of colorectal cancer in mice

Lucia Recinella, Annalisa Chiavaroli, Serena Veschi, Valentina Di Valerio, Rossano Lattanzio, Giustino Orlando, Claudio Ferrante, Iacopo Gesmundo, Riccarda Granata, Renzhi Cai, Wei Sha, Andrew V. Schally, Luigi Brunetti, Sheila Leone

Research output: Contribution to journalArticlepeer-review

Abstract

Colorectal cancer (CRC) is an aggressive tumor in which new treatment options deliver negative results on cure rates and long-term survival. The anticancer effects of growth hormone-releasing hormone (GHRH) antagonists have been reported in various experimental tumors, but their activity in CRC is unknown. In the present study, we demonstrated that chronic treatment with GHRH antagonist of MIAMI class, MIA-690, promoted survival and gradually blunted tumor progression in experimentally induced colitis-associated cancer in mice, paralleled by reduced inflammation in colon tissue. In particular, MIA-690 improved disease activity index score, and reduced loss of weight and mortality, by improving the survival rates, compared with vehicle-treated group. MIA-690 was also found to reduce various inflammatory and oxidative markers, such as serotonin, prostaglandin (PG)E2 and 8-iso-PGF levels, as well as COX-2, iNOS, TNF-α, IL-6 and NF-kB gene expression. Moreover, MIA-690 inhibited the protein expression of c-Myc, P-AKT and Bcl-2 and upregulated p53 protein expression. In conclusion, we showed that MIA-690 suppresses CRC progression and growth by reducing inflammatory and oxidative markers and modulating apoptotic and oncogenic pathways. Further investigations are required for translating these findings into the clinics.

Original languageEnglish (US)
Article number112554
JournalBiomedicine and Pharmacotherapy
Volume146
DOIs
StatePublished - Feb 2022
Externally publishedYes

Keywords

  • Apoptotic pathways
  • Colorectal cancer
  • Growth hormone-releasing hormone antagonist
  • Inflammation
  • Oncogenic pathways
  • Oxidative stress

ASJC Scopus subject areas

  • Pharmacology

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