In vitro and in vivo anti-colorectal cancer effect of the newly synthesized sericin/propolis/fluorouracil nanoplatform through modulation of PI3K/AKT/mTOR pathway.
Sci Rep
; 14(1): 2433, 2024 01 29.
Article
en En
| MEDLINE
| ID: mdl-38286826
ABSTRACT
The present work aimed to assess the potential effect of sericin/propolis/fluorouracil nanoformula against colorectal cancer (CRC) (the fourth most common cause of cancer-related mortalities). A novel anti-cancerous formula of the synthesized sericin/propolis nanoparticles was developed and tested both in vitro (using Caco-2 cell line) and in vivo (in experimentally induced colorectal cancer animal models). The combination index of the prepared nanoformula proved that the combination between sericin/propolis nanoparticles and 5-fluorouracil demonstrated the highest synergistic effect (0.86), with dose reduction index (DRI) of the chemotherapeutic drug reaching 1.49. The mechanism of action of the prepared nanoformula revealed that it acts through the inhibition of the PI3K/AKT/mTOR signaling pathway and consequently inhibiting cancerous cells proliferation. Treatment and prophylactic studies of both sericin and propolis showed increased TBARS (Thiobarbituric Acid Reactive Substance) formation, downregulated BCL2 (B-cell lymphoma 2) and activated BAX, Caspase 9 and Caspase 3 expression. The prepared nanoformula decreased the ROS (Reactive Oxygen Species) production in vivo owing to PI3K/AKT/mTOR pathway inhibition and FOXO-1 (Forkhead Box O1) activation that resulted in autophagy/apoptosis processes stimulation. The potent anticancer effect of the prepared nanoformula was further emphasized through the in vivo histopathological studies of experimentally induced tumors. The newly formulated sericin/propolis/fluorouracil nanoparticles exhibited clear-cut cytotoxic effects toward tumor cells with provided evidence for the prophylactic effect.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_colon_rectum_cancers
Asunto principal:
Própolis
/
Neoplasias Colorrectales
/
Sericinas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
Egipto