Almorexant, an Orexin Antagonist with Anti-Tumoral Properties in Human Colon Cancer

Author Info

S. Dayot V. Gratio P. Nicole T. Voisin Alain Couvineau

Corresponding Author

Alain Couvineau
INSERM UMR1149/ Inflammation Research Center (CRI), Team “From inflammation to cancer in digestive diseases” labeled by “la Ligue Nationale Contre le Cancer”, University of Paris, DHU UNITY, Paris, France

A B S T R A C T

Colorectal cancer, which is the third most common cancer, is the main cause of digestive cancer death. Previous studies have demonstrated that orexins, hypothalamic neuropeptides involved in sleep and food intake regulations, have anti-tumoral properties in digestive cancers. In the present work, we investigated the anti-tumoral role of an orexin antagonist, almorexant, in colon cancer. The anti-tumoral role of almorexant has been determined by in vitro and in vivo studies using HT-29 colon cancer cell line, which expressed endogenous orexin receptor 1 subtype (OX1R). Our in vitro study indicated that almorexant was able to reduce HT-29 cell viability by induction of mitochondrial apoptosis involving the tyrosine phosphatase SHP2 and the p38 signaling pathways. In contrast, no effect was observed in the colon cancer cell line HCT-116, which does not express OX1R, demonstrating that the anti-tumoral effect of almorexant was mediated by OX1R. When HT-29 cells were xenografted in nude mice, the administration of almorexant strongly reduced the tumor development with a potency similar to orexin. Our study supports that almorexant, a small molecule analog of orexin peptide, could represent a putative candidate in the treatment of colorectal cancer.

Article Info

Article Type

Research Article

Publication history

Received: Thu 23, Apr 2020
Accepted: Mon 08, Jun 2020
Published: Fri 24, Jul 2020

Copyright

© 2023 Alain Couvineau. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.EJMC.2020.01.02