FDA-approved antivirals ledipasvir and daclatasvir downregulate the Src-EPHA2-Akt oncogenic pathway in colorectal and triple-negative breast cancer cells.
Biomed Pharmacother
; 179: 117325, 2024 Oct.
Article
de En
| MEDLINE
| ID: mdl-39226729
ABSTRACT
Direct-acting antivirals ledipasvir (LDV) and daclatasvir (DCV) are widely used as part of combination therapies to treat Hepatitis C infections. Here we show that these compounds inhibit the proliferation, invasion, and colony formation of triple-negative MDA-MB-231 breast cancer cells, SRC-transduced SW620 colon cancer cells and SRC- transduced NIH3T3 fibroblasts. DCV also inhibits the expression of PDL-1, which is responsible for resistance to immunotherapy in breast cancer cells. The demonstrated low toxicity in many Hepatitis C patients suggests LDV and DCV could be used in combination therapies for cancer patients. At the molecular level, these direct-acting antivirals inhibit the phosphorylation of Akt and the ephrin type A receptor 2 (EPHA2) by destabilizing a Src-EPHA2 complex, although they do not affect the general kinase activity of Src. Thus, LDV and DCV could be effective drugs for Src-associated cancers without the inherent toxicity of classical Src inhibitors.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Antiviraux
/
Pyrrolidines
/
Valine
/
Benzimidazoles
/
Carbamates
/
Tumeurs colorectales
/
Transduction du signal
/
Régulation négative
/
Src-Family kinases
/
Protéines proto-oncogènes c-akt
Limites:
Animals
/
Female
/
Humans
Pays/Région comme sujet:
America do norte
Langue:
En
Journal:
Biomed Pharmacother
Année:
2024
Type de document:
Article
Pays de publication:
France