FH535 suppresses the proliferation and motility of hepatocellular carcinoma cells

Tomizawa, M.; Shinozaki, Fuminobu; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shozo; Ishige, Naoki

doi:10.3892/ijo.2015.3220

Cited by 7 publications

(4 citation statements)

References 21 publications

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“…FH535 is a dual small molecule inhibitor of peroxisome proliferator-activated receptors (PPARs) and β-catenin/TCF/LEF 10 . Previous studies demonstrated that FH535 inhibits the growth of colon, lung, breast, pancreatic and hepatocellular cancer cells 10 - 13 , and represses pancreatic cancer xenograft growth and angiogenesis 14 .…”

Section: Introductionmentioning

confidence: 99%

FH535 Inhibits Proliferation and Motility of Colon Cancer Cells by Targeting Wnt/β-catenin Signaling Pathway

Chen¹,

Rao²,

Huang³

et al. 2017

J. Cancer

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Aberrant Wnt/β-catenin pathway activation is frequently observed in human colorectal cancer (CRC) and has become a promising target for CRC treatment. Our study aimed to evaluate the effect of FH535, a small molecule inhibitor of Wnt/β-catenin pathway, on two colon cancer cell lines, HT29 and SW480. We found FH535 significantly inhibited colon cancer cell proliferation in vitro and induced cell cycle arrest. Moreover, FH535 inhibited colon cancer xenograft growth in vivo. Wound-healing assay and Transwell assay revealed that FH535 notably suppressed migration and invasion of SW480 cells. FH535 also repressed expression of cancer stem cell markers, CD24, CD44 and CD133 in HT29 cells. Real time-quantitative PCR and Western blotting revealed that targeting Wnt/β-catenin pathway using FH535 effectively downregulated target genes including cyclin D1 and survivin at mRNA and protein level, which contributed to the FH535-induced inhibitory effect on colon cancer cell proliferation. As mechanisms for suppressing cancer cell motility, FH535 downregulated expression of matrix metalloproteinase-7 and -9, Snail and vimentin. RNA sequencing revealed that FH535 prominently altered multiple biological pathways associated with DNA replication, cell cycle and metabolism. Our study highlights the anti-cancer effect of FH535 on colon cancer and presents its potential in colon cancer treatment.

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Section: Introductionmentioning

confidence: 99%

FH535 Inhibits Proliferation and Motility of Colon Cancer Cells by Targeting Wnt/β-catenin Signaling Pathway

Chen¹,

Rao²,

Huang³

et al. 2017

J. Cancer

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“…BLBP expression has been correlated with poor clinical outcome in several aggressive forms of cancer, such as renal cancer [ 22 ], hepatocellular carcinoma [ 30 ] and aggressive triple-negative breast cancer [ 31 ]. Since CSCs contribute to the aggressive nature of tumours and BLBP was a marker for these CSCs in ependymoma, we proposed that BLBP expression could be of robust prognostic value in ependymoma, a tumour for which prognostic markers are urgently required.…”

Section: Discussionmentioning

confidence: 99%

BLBP Is Both a Marker for Poor Prognosis and a Potential Therapeutic Target in Paediatric Ependymoma

Sabnis

Liu

Simmonds

et al. 2021

Cancers

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Paediatric ependymomas are aggressive, treatment-resistant tumours with a tendency towards relapse, consistent with a sub-population of therapy-resistant cancer stem cells. These cells are believed to derive from brain lipid binding protein (BLBP)-expressing radial glia, hence we proposed that BLBP may be a marker for ependymoma therapy resistance. BLBP protein expression correlated with reduced overall survival (OS) in patients from two trials (CNS9204, a chemotherapy-led infant trial—5 y OS 45% vs. 80%, p = 0.011—and CNS9904, a radiotherapy-led trial—OS 38% vs. 85%, p = 0.002). All ependymoma cell lines examined by qRT-PCR expressed BLBP, with expression elevated in stem cell-enriched neurospheres. Modulation of BLBP function in 2D and 3D assays, using either peroxisome proliferator activated receptor (PPAR) antagonists or BLBP’s fatty acid substrate docosahexaneoic acid (DHA), potentiated chemotherapy response and reduced cell migration and invasion in ependymoma cell lines. BLBP is therefore an independent predictor of poor survival in paediatric ependymoma, and treatment with PPAR antagonists or DHA may represent effective novel therapies, preventing chemotherapy resistance and invasion in paediatric ependymoma patients.

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“…FH535 is another antagonist that inhibits the Wnt/β-catenin signaling pathway and peroxisome proliferator-activator receptor (PPARγ and PPARδ) signaling [ 126 ]. This compound suppresses proliferation and motility of HCC cells through significant downregulation of cyclin D1 and MMP9 mRNA [ 127 ]. Additionally, FH535 is a potent therapeutic inhibitor that, upon combination with Sorafenib, exerts synergistic inhibition of proliferation and induction of apoptosis via enhancing cleaved poly (ADP-ribose) polymerase (PARP), inhibiting cyclin D1, Bcl-2, survivin, and c-MYC levels and reducing both mitochondrial respiration and glycolytic rates to disrupt the bioenergetics of HCC/LCSC cells [ 128 , 129 ].…”

Section: Interactions Of Lcscs Influencing Hcc and Therapeutic Strmentioning

confidence: 99%

Cancer Stem Cell Functions in Hepatocellular Carcinoma and Comprehensive Therapeutic Strategies

Liu

Yeh

Lin

2020

Cells

190

134

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Hepatocellular carcinoma (HCC) is a significant cause of cancer-related mortality owing to resistance to traditional treatments and tumor recurrence after therapy, which leads to poor therapeutic outcomes. Cancer stem cells (CSC) are a small subset of tumor cells with the capability to influence self-renewal, differentiation, and tumorigenesis. A number of surface markers for liver cancer stem cell (LCSC) subpopulations (EpCAM, CD133, CD44, CD13, CD90, OV-6, CD47, and side populations) in HCC have been identified. LCSCs play critical roles in regulating HCC stemness, self-renewal, tumorigenicity, metastasis, recurrence, and therapeutic resistance via genetic mutations, epigenetic disruption, signaling pathway dysregulation, or alterations microenvironment. Accumulating studies have shown that biomarkers for LCSCs contribute to diagnosis and prognosis prediction of HCC, supporting their utility in clinical management and development of therapeutic strategies. Preclinical and clinical analyses of therapeutic approaches for HCC using small molecule inhibitors, oncolytic measles viruses, and anti-surface marker antibodies have demonstrated selective, efficient, and safe targeting of LCSC populations. The current review focuses on recent reports on the influence of LCSCs on HCC stemness, tumorigenesis, and multiple drug resistance (MDR), along with LCSC-targeted therapeutic strategies for HCC.

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FH535 suppresses the proliferation and motility of hepatocellular carcinoma cells

Cited by 7 publications

References 21 publications

FH535 Inhibits Proliferation and Motility of Colon Cancer Cells by Targeting Wnt/β-catenin Signaling Pathway

FH535 Inhibits Proliferation and Motility of Colon Cancer Cells by Targeting Wnt/β-catenin Signaling Pathway

BLBP Is Both a Marker for Poor Prognosis and a Potential Therapeutic Target in Paediatric Ependymoma

Cancer Stem Cell Functions in Hepatocellular Carcinoma and Comprehensive Therapeutic Strategies

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