Phloretin-induced STAT3 inhibition suppresses pancreatic cancer growth and progression via enhancing Nrf2 activity.
Phytomedicine
; 118: 154990, 2023 Sep.
Article
em En
| MEDLINE
| ID: mdl-37494874
ABSTRACT
BACKGROUND:
Pancreatic ductal adenocarcinoma (PDAC) is a malignant pancreatic tumor charactered by a rapid progression and high lethal rate. Hyperactivation of STAT3 signaling exerts a vital effect on the growth and progression of PDAC. While dietary flavonoid phloretin has anti-inflammatory and antioxidant activities, it remains unclear whether phloretin has anti-tumor effects on PDAC.PURPOSE:
The focus of the present study is to elucidate the effects of phloretin on PDAC and investigate its underlying molecular mechanisms. STUDY DESIGN ANDMETHODS:
Effect of phloretin were assessed in the pancreatic cancer cells (PCCs) by colony formation assay, real-time cell analysis, flow cytometry, Immunofluorescence staining, and cell migration assay. The expressions of mRNA and protein were respectively analyzed by quantitative PCR and Western blotting. A xenograft model was used to appraise the antitumor efficacy of phloretin.RESULTS:
Phloretin treatment significantly restrained cell viability and metastasis, induced DNA injury and ROS accumulation, and triggered mitochondrial-dependent apoptosis in PCCs. Mechanistically, phloretin exhibits anti-tumor potential via inactivating STAT3 signaling and enhancing Nrf2 activity. STAT3 overexpression and Nrf2 silencing partially relieved phloretin-induced inhibition on cell growth and metastasis in PCCs. Phloretin remarkably blocked pancreatic tumor growth and metastasis in vivo.CONCLUSIONS:
Phloretin suppresses pancreatic cancer growth and progression through inhibition of STAT3 mediated by enhancing Nrf2 activity. Phloretin may serve as a promising therapeutic agent for PDAC.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Carcinoma Ductal Pancreático
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Phytomedicine
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2023
Tipo de documento:
Article