Daidzein Suppresses Tumor Necrosis Factor-α Induced Migration and Invasion by Inhibiting Hedgehog/Gli1 Signaling in Human Breast Cancer Cells

Bao, Cheng; Namgung, Hyeju; Lee, Jaehoo; Park, Hyun‐Chang; Ko, Jiwon; Moon, Hee-Jung; Ko, Hyuk Wan; Lee, Hong Jin

doi:10.1021/jf500231t

Cited by 40 publications

(29 citation statements)

References 43 publications

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“…However, the irresponsiveness of TNF-α on CCA cell line (KKU-100) proliferation is still unclear and needs further investigation. Additionally, TNF-α can facilitate cancer cell invasion and has been investigated in breast cell lines (Ryu et al, 2011) and glioma cell lines (Bao et al, 2014). The results of our invasion assay supported that TNF-α also affected invasiveness of CCA cell line with dose-and time dependence.…”

Section: Discussionsupporting

confidence: 75%

ALCAM is a Novel Cytoplasmic Membrane Protein in TNF-α Stimulated Invasive Cholangiocarcinoma Cells

Adisakwattana

Suwandittakul²,

Petmitr³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Cholangiocarcinoma (CCA), or bile duct cancer, is incurable with a high mortality rate due to a lack of effective early diagnosis and treatment. Identifying cytoplasmic membrane proteins of invasive CCA that facilitate cancer progression would contribute toward the development of novel tumor markers and effective chemotherapy. Materials and Methods: An invasive CCA cell line (KKU-100) was stimulated using TNF-α and then biotinylated and purified for mass spectrometry analysis. Novel proteins expressed were selected and their mRNAs expression levels were determined by real-time RT-PCR. In addition, the expression of ALCAM was selected for further observation by Western blot analysis, immunofluorescent imaging, and antibody neutralization assay. Results: After comparing the proteomics profile of TNF-α induced invasive with non-treated control cells, over-expression of seven novel proteins was observed in the cytoplasmic membrane of TNF-α stimulated CCA cells. Among these, ALCAM is a novel candidate which showed significant higher mRNA-and protein levels. Immunofluorescent assay also supported that ALCAM was expressed on the cell membrane of the cancer, with increasing intensity associated with TNF-α. Conclusions: This study indicated that ALCAM may be a novel protein candidate expressed on cytoplasmic membranes of invasive CCA cells that could be used as a biomarker for development of diagnosis, prognosis, and drug or antibody-based targeted therapies in the future.

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Section: Discussionsupporting

confidence: 75%

ALCAM is a Novel Cytoplasmic Membrane Protein in TNF-α Stimulated Invasive Cholangiocarcinoma Cells

Adisakwattana

Suwandittakul²,

Petmitr³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…Consistent with this, Hh regulation of cell motility and inhibition of cell migration by blocking Hh signaling have been documented under various pathophysiological circumstances. [42][43][44][45] Overall, Hh signaling could be a therapeutic target for reduction of HSC activation and inhibition of profibrogenic behaviors of activated HSCs.…”

Section: Discussionmentioning

confidence: 99%

Curcumin regulates cell fate and metabolism by inhibiting hedgehog signaling in hepatic stellate cells

Lian

Jiang

Zhang

et al. 2015

Laboratory Investigation

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Accumulating evidence indicates that Hedgehog (Hh) signaling becomes activated in chronic liver injury and plays a role in the pathogenesis of hepatic fibrosis. Hepatic stellate cells (HSCs) are Hh-responsive cells and activation of the Hh pathway promotes transdifferentiation of HSCs into myofibroblasts. Targeting Hh signaling may be a novel therapeutic strategy for treatment of liver fibrosis. We previously reported that curcumin has potent antifibrotic effects in vivo and in vitro, but the underlying mechanisms are not fully elucidated. This study shows that curcumin downregulated Patched and Smoothened, two key elements in Hh signaling, but restored Hhip expression in rat liver with carbon tetrachlorideinduced fibrosis and in cultured HSCs. Curcumin also halted the nuclear translocation, DNA binding, and transcription activity of Gli1. Moreover, the Hh signaling inhibitor cyclopamine, like curcumin, arrested the cell cycle, induced mitochondrial apoptosis, reduced fibrotic gene expression, restored lipid accumulation, and inhibited invasion and migration in HSCs. However, curcumin's effects on cell fate and fibrogenic properties of HSCs were abolished by the Hh pathway agonist SAG. Furthermore, curcumin and cyclopamine decreased intracellular levels of adenosine triphosphate and lactate, and inhibited the expression and/or function of several key molecules controlling glycolysis. However, SAG abrogated the curcumin effects on these parameters of glycolysis. Animal data also showed that curcumin downregulated glycolysis-regulatory proteins in rat fibrotic liver. These aggregated data therefore indicate that curcumin modulated cell fate and metabolism by disrupting the Hh pathway in HSCs, providing novel molecular insights into curcumin reduction of HSC activation.

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“…Aberrant Hh activation has been demonstrated in breast, colon, and prostate cancer (10)(11)(12), and is closely associated with self-renewal, invasion and migration of cancer stem cells, promoting cancer progression (13,14). It was reported that Hh signaling might induce EMT in pancreatic cancer (9,15).…”

Section: Introductionmentioning

confidence: 99%

Casticin inhibits the epithelial-mesenchymal transition in ovarian carcinoma via the hedgehog signaling pathway

et al. 2018

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Abstract. Casticin inhibits migration, invasion and induced apoptosis in numerous cancer cells; however, the Hedgehog (Hh) signaling pathway is a key factor in the epithelial-mesenchymal transition (EMT). The present study aimed to assess whether casticin affects the expression of members of the Hh signaling pathway and EMT effectors in ovarian carcinoma. The ovarian cancer SKOV3 cell line was incubated in the presence of various concentrations of casticin or cyclopamine. Next, the expression levels of the main Hh signaling effector glioma-associated oncogene-1 (Gli-1) and EMT-associated factors [Twist-related protein 1 (Twist1), E-cadherin and N-cadherin] were determined by western blotting and reverse transcription-quantitative polymerase chain reaction. Cell proliferation and growth were assessed using MTT and soft agar assays; cell migration and invasion was evaluated using an in vitro migration assay and a transwell invasion assay, respectively. Compared with control group values, Gli-1, Twist1 and N-cadherin expression levels were reduced, whereas E-cadherin levels were increased in the casticin-and cyclopamine-treated groups. Incubation with casticin or cyclopamine resulted in markedly reduced SKOV3 cell viability, migration and invasion, in a dose-dependent manner. To the best of our knowledge, the findings of the present study indicated for first time that casticin may inhibit EMT via Hh signaling in vitro, reducing the migratory ability of ovarian cancer cells.

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Daidzein Suppresses Tumor Necrosis Factor-α Induced Migration and Invasion by Inhibiting Hedgehog/Gli1 Signaling in Human Breast Cancer Cells

Cited by 40 publications

References 43 publications

ALCAM is a Novel Cytoplasmic Membrane Protein in TNF-α Stimulated Invasive Cholangiocarcinoma Cells

ALCAM is a Novel Cytoplasmic Membrane Protein in TNF-α Stimulated Invasive Cholangiocarcinoma Cells

Curcumin regulates cell fate and metabolism by inhibiting hedgehog signaling in hepatic stellate cells

Casticin inhibits the epithelial-mesenchymal transition in ovarian carcinoma via the hedgehog signaling pathway

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