Preclinical evaluation of dalbergin loaded PLGA-galactose-modified nanoparticles against hepatocellular carcinoma via inhibition of the AKT/NF-κB signaling pathway.
Int Immunopharmacol
; 140: 112813, 2024 Oct 25.
Article
en En
| MEDLINE
| ID: mdl-39088916
ABSTRACT
Prior research has shown the effectiveness of dalbergin (DL), dalbergin nanoformulation (DLF), and dalbergin-loaded PLGA-galactose-modified nanoparticles (DLMF) in treating hepatocellular carcinoma (HCC) cells. The present investigation constructs upon our previous research and delves into the molecular mechanisms contributing to the anticancer effects of DLF and DLMF. This study examined the anti-cancer effects of DL, DLF, and DLMF by diethyl nitrosamine (DEN)-induced HCC model in albino Wistar rats. In addition, we performed biochemical, antioxidant, lipid profile tests, and histological studies of liver tissue. The anticancer efficacy of DLMF is equivalent to that of 5-fluorouracil, a commercially available therapy for HCC. Immunoblotting studies revealed a reduction in the expression of many apoptotic markers, such as p53, BAX, and Cyt-C, in HCC. Conversely, the expression of Bcl-2, TNF-α, NFκB, p-AKT, and STAT-3 was elevated. Nevertheless, the administration of DL, DLF, and DLMF effectively controlled the levels of these apoptotic markers, resulting in a considerable decrease in the expression of Bcl-2, TNF-α, NFκB, p-AKT, and STAT-3. Specifically, the activation of TNF-alpha and STAT-3 triggers the signalling pathways that include the Bcl-2 family of proteins, Cyt-C, caspase 3, and 9. This ultimately leads to apoptosis and the suppression of cell growth. Furthermore, metabolomic analysis using 1H NMR indicated that the metabolites of animals reverted to normal levels after the treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Apoptosis
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Carcinoma Hepatocelular
/
Nanopartículas
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Copolímero de Ácido Poliláctico-Ácido Poliglicólico
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Galactosa
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Neoplasias Hepáticas
/
Antineoplásicos
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Int Immunopharmacol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Países Bajos