Daidzin targets epithelial-to-mesenchymal transition process by attenuating manganese superoxide dismutase expression and PI3K/Akt/mTOR activation in tumor cells.
Life Sci
; 295: 120395, 2022 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-35181309
AIMS: Epithelial-mesenchymal transition (EMT) is a process during which epithelial cells lose their polarity and gain invasive properties to transform into mesenchymal cells. A few recent studies have reported that manganese superoxide dismutase (MnSOD) can effectively modulate EMT phenotype by influencing cellular redox environment via altering the intracellular ratio between O2- and H2O2. Daidzin (DDZ), a naturally occurring isoflavone isolated from Pueraria lobate (Fabaceae), has numerous pharmacologic effects including anti-cholesterol, anti-angiocardiopathy, anti-cancer. However, the potential inhibitory impact of DDZ on cancer metastasis and specifically on the EMT process has not been evaluated. We aimed to evaluate the possible relationship between MnSOD and EMT as well as influence of DDZ on these two processes in colon and prostate carcinoma cells. MAIN METHODS: Cell viability was measured by MTT and real time cell analysis (RTCA) assay. Protein expression level of EMT markers and Akt/mTOR/PI3K signaling pathway were evaluated by Western blot analysis. Expression of EMT markers in cells was observed by immunocytochemistry. Cell invasion and migrations were evaluated by wound healing assay and Boyden chamber assay. KEY FINDINGS: DDZ can block EMT accompanied with down-regulation of MnSOD, fibronectin, vimentin, MMP-9, MMP-2, N-cadherin, twist, and Snail, and up-regulation of occludin and E-cadherin in both unstimulated and TGFß-induced cells. In addition, DDZ exposure also attenuated cell proliferation, invasion, and metastasis by reversing the EMT process in SNU-C2A, DU145, and PC-3 cells. DDZ treatment also modulated activation of PI3K/Akt/mTOR signaling cascades in DU145 cells. Moreover, an overexpression of MnSOD or silencing of MnSOD expression modulated EMT-related proteins, PI3K/Akt/mTOR activation and invasive activity. SIGNIFICANCE: This is first finding on the DDZ in regulating MnSOD and EMT process by targeting PI3K/Akt/mTOR pathway in both colorectal and prostate cancer cell lines. Our data indicated that DDZ might act as a potent suppressor of EMT by affecting MnSOD expression in tumor cells.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Superóxido Dismutasa
/
Transición Epitelial-Mesenquimal
/
Isoflavonas
Límite:
Humans
Idioma:
En
Revista:
Life Sci
Año:
2022
Tipo del documento:
Article
Pais de publicación:
Países Bajos