Targeting the Wnt/β-Catenin Signaling Pathway in Liver Cancer Stem Cells and Hepatocellular Carcinoma Cell Lines with FH535

Gedaly, Roberto; Galuppo, Roberto; Daily, Michael F.; Shah, Malay B.; Maynard, Erin; Chen, Changguo; Zhang, Xiping; Esser, Karyn A.; Cohen, Donald A.; Evers, B. Mark; Jiang, Jieyun; Spear, Brett T.

doi:10.1371/journal.pone.0099272

Cited by 97 publications

(73 citation statements)

References 36 publications

(47 reference statements)

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“…The expression levels of cyclin D1 decreased in both cell types after incubation with FH535. In the HCC cells, FH535 decreased the expression levels of cyclin D1 and suppressed the cell cycle (19). These results were consistent with those of the previous reports.…”

Section: Discussionsupporting

confidence: 93%

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FH535 suppresses the proliferation and motility of hepatocellular carcinoma cells

Tomizawa

Shinozaki

Motoyoshi

et al. 2015

International Journal of Oncology

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Abstract. The Wnt signaling pathway is activated in hepatocellular carcinoma (HCC). This study investigated the effects of FH535, an inhibitor of the Wnt signaling pathway, on the proliferation and motility of HCC cells. HLF cells and PLC/ PRF/5 cells, HCC cells, were subjected to 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay with the addition of FH535. RNA was isolated from the cells and subjected to real-time quantitative PCR. Hematoxylin and eosin (H&E) staining was performed to analyze apoptosis. A scratch assay was performed to analyze cell motility. Cell proliferation significantly decreased (P<0.05). The expression levels of cyclin D1 significantly decreased in both cell lines (P<0.05). Pyknotic nuclei were observed in the cells cultured with FH535 (50 µM). In the scratch assay, the distance between the growing edges of cells and the scratched line significantly decreased with the addition of FH535 at 50 µM (P<0.05). The expression levels of matrix metalloproteinase 9 significantly decreased at 50 µM (P<0.05). FH535 suppressed the proliferation of HCC cells by downregulating the expression of cyclin D1 and by inducing apoptosis. Further, it suppressed cell motility by downregulating the expression of matrix metalloproteinase.

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Section: Discussionsupporting

confidence: 93%

“…In addition, FH535 is known to suppress the metastasis of HCC and pancreatic cancer cells (19,20). In this study, the expression levels of matrix metalloproteinase 9 decreased in HLF cells and PLC/PRF/5 cells.…”

Section: Discussionmentioning

confidence: 99%

FH535 suppresses the proliferation and motility of hepatocellular carcinoma cells

Tomizawa

Shinozaki

Motoyoshi

et al. 2015

International Journal of Oncology

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“…83 Aberrant activation of the Wnt/β-catenin signaling has recently been implicated in several types of cancers, including ovarian, 84 colon, 85 and breast cancer. 86 Interestingly, this signaling pathway was initially reported as a key CSC signaling pathway in acute myeloid leukemia 87 and was reported to be involved in the maintenance and function of CSCs from breast, 88 colon, 89 liver, 90 and lung 91 cancers. Therefore, selective targeting of Wnt/β-catenin signaling may be considered as an effective therapeutic strategy for the treatment of various types of cancer.…”

Section: Cd133mentioning

confidence: 99%

Targeting cancer stem cells by using the nanoparticles

Hong

Jang

Lee

et al. 2015

IJN

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Cancer stem cells (CSCs) have been shown to be markedly resistant to conventional cancer treatments such as chemotherapy and radiation therapy. Therefore, therapeutic strategies that selectively target CSCs will ultimately lead to better cancer treatments. Currently, accessible conventional therapeutic agents mainly eliminate the bulk tumor but do not eliminate CSCs. Therefore, the discovery and improvement of CSC-targeting therapeutic agents are necessary. Nanoparticles effectively inhibit multiple types of CSCs by targeting specific signaling pathways (Wnt/β-catenin, Notch, transforming growth factor-β, and hedgehog signaling) and/or specific markers (aldehyde dehydrogenases, CD44, CD90, and CD133) critically involved in CSC function and maintenance. In this review article, we summarized a number of findings to provide current information about their therapeutic potential of nanoparticles in various cancer cell types and CSCs.

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“…For example, the expression level of β-catenin has been shown to correlate with progression in colorectal (18), cervical (19) and prostate cancer (20). The activation of β-catenin was also involved in various stages of hepatic carcinoma (21)(22)(23)(24) and cholangiocarcinoma (25,26). β-catenin leads to the activation of target genes such as c-Myc (27), Snail (28) and cyclin D1 (29).…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin E2 promotes human cholangiocarcinoma cell proliferation, migration and invasion through the upregulation of β-catenin expression via EP3-4 receptor

Feng

Zhang

et al. 2015

Oncology Reports

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Abstract. Prostaglandin E2 (PGE2) is involved in cholangiocarcinoma cell proliferation, migration and invasion through E prostanoid receptors, including EP1, EP2 and EP4. However, the functions and the mechanisms of those splice variants of EP3 receptors in promoting liver cancer cell growth and invasion remain to be elucidated. In our previous studies, four isoforms of EP3 receptors, EP3-4, EP3-5, EP3-6 and EP3-7 receptors, were detected in CCLP1 and HuCCT1 cells. However, the functions of these receptors in these cells have yet to be determined. It was reported that β-catenin is closely correlated with malignancy, including cholangiocarcinoma. The present study was designed to examine the effects of 4-7 isoforms of EP3 in promoting cholangiocarcinoma progression and the mechanisms by which PGE2 increases β-catenin protein via EP3 receptors. The results showed that PGE2 promotes cholangiocarcinoma progression via the upregulation of β-catenin protein, and the EP3-4 receptor pathway is mainly responsible for this regulation. These findings reveal that PGE2 upregulated the cholangiocarcinoma cell β-catenin protein through the EP3-4R/Src/EGFR/PI3K/AKT/GSK-3β pathway. The present study identified the functions of EP3 and the mechanisms by which PGE2 regulates β-catenin expression and promoted cholangiocarcinoma cell growth and invasion.

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Targeting the Wnt/β-Catenin Signaling Pathway in Liver Cancer Stem Cells and Hepatocellular Carcinoma Cell Lines with FH535

Cited by 97 publications

References 36 publications

FH535 suppresses the proliferation and motility of hepatocellular carcinoma cells

FH535 suppresses the proliferation and motility of hepatocellular carcinoma cells

Targeting cancer stem cells by using the nanoparticles

Prostaglandin E2 promotes human cholangiocarcinoma cell proliferation, migration and invasion through the upregulation of β-catenin expression via EP3-4 receptor

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