Dataset Information

Naringenin decreases invasiveness and metastasis by inhibiting TGF-?-induced epithelial to mesenchymal transition in pancreatic cancer cells.

ABSTRACT: Epithelial to mesenchymal transition (EMT) promotes cellular motility, invasiveness and metastasis during embryonic development and tumorigenesis. Transforming growth factor-? (TGF-?) signaling pathway is a key regulator of EMT. A lot of evidences suggest that this process is Smad3-dependent. Herein we showed that exposure of aspc-1 and panc-1 pancreatic cancer cells to TGF-?1 resulted in characteristic morphological alterations of EMT, and enhancement of cell motility and gemcitabine (Gem) resistance along with an up-regulation of EMT markers genes such as vimentin, N-cadherin, MMP2 and MMP9. Naringenin (Nar) down-regulated EMT markers expression in both mRNA and protein levels by inhibiting TGF-?1/Smad3 signal pathway in the pancreatic cancer cells. Consequently, Nar suppressed the cells migration and invasion and reversed their resistance to Gem.

SUBMITTER: Lou C

PROVIDER: S-EPMC3530567 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Naringenin decreases invasiveness and metastasis by inhibiting TGF-β-induced epithelial to mesenchymal transition in pancreatic cancer cells.

Lou Changjie C Zhang Fayun F Yang Ming M Zhao Juan J Zeng Wenfeng W Fang Xiaocui X Zhang Yanqiao Y Zhang Chunling C Liang Wei W

PloS one 20121226 12

Epithelial to mesenchymal transition (EMT) promotes cellular motility, invasiveness and metastasis during embryonic development and tumorigenesis. Transforming growth factor-β (TGF-β) signaling pathway is a key regulator of EMT. A lot of evidences suggest that this process is Smad3-dependent. Herein we showed that exposure of aspc-1 and panc-1 pancreatic cancer cells to TGF-β1 resulted in characteristic morphological alterations of EMT, and enhancement of cell motility and gemcitabine (Gem) resi ...[more]

PMID: 23300530

Similar Datasets

Project description:Deguelin is known to suppress the growth of cancer cells; however, its anti-metastatic effects have not been studied so far in any cancer model. In the present study, we aimed to evaluate the anti-metastatic potential of deguelin in vivo and in tumor growth factor-β1 (TGFβ1)-stimulated cells. Our results demonstrate that tumor growth, peritoneal dissemination and liver/lung metastasis of orthotopically implanted PanC-1-luc cells were significantly reduced in deguelin-treated mice along with the induction of apoptosis. Furthermore, deguelin-treated tumors showed increased epithelial signature such as increased expression of E-Cadherin and cytokeratin-18 and decreased expression of Snail. Similar observations were made when PanC-1, COLO-357 and L3.6pl cells were treated in vitro with deguelin. Moreover, E-cadherin was transcriptionally upregulated and accumulated in the membrane fraction of deguelin-treated cells, as indicated by increased interaction of E-Cadherin with β-catenin. TGFβ1-induced downregulation of E-Cadherin and upregulation of Snail were abrogated by deguelin treatment. In addition, deguelin inhibited TGFβ1-induced Smad3 phosphorylation and Smad4 nuclear translocation in PanC-1 cells. Furthermore, when TGFβ1-induced nuclear factor kappa B (NFκB) activation was inhibited, TGFβ1-induced Snail upregulation or E-Cadherin downregulation was blocked. Deguelin also significantly downregulated the constitutive phosphorylation and DNA binding of NFκB in a dose-dependent manner. Interestingly, overexpression of either NFκB or Snail completely abrogated deguelin-mediated epithelial-to-mesenchymal transition (EMT) inhibition, whereas overexpression of NFκB but not Snail rescued cells from deguelin-induced apoptosis. Hence, deguelin targets NFκB to induce reversal of EMT and apoptosis but downstream effectors might be different for both processes. Taken together, our results suggest that deguelin suppresses both pancreatic tumor growth and metastasis by inducing apoptosis and inhibiting EMT.

Dataset Information

Naringenin decreases invasiveness and metastasis by inhibiting TGF-?-induced epithelial to mesenchymal transition in pancreatic cancer cells.

Publications

Naringenin decreases invasiveness and metastasis by inhibiting TGF-β-induced epithelial to mesenchymal transition in pancreatic cancer cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets