N-Myc down-regulated gene 1 mediates proliferation, invasion, and apoptosis of hepatocellular carcinoma cells

Yan, Xinrui; Chua, Mei-Sze; Sun, Hongbo; So, Samuel

doi:10.1016/j.canlet.2007.12.010

Cited by 51 publications

(35 citation statements)

References 25 publications

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“…3A), which was contrary to a previous observation with other iron chelators in some other types of cancer cells (28). Although Ndrg1 suppress metastasis in some cancers, Ndrg1 was oncogenic in HCC and knockdown Ndrg1 could inhibit tumor growth (29). This suggested that TSC24 may act in a tissue-specific way.…”

Section: Tsc24 Affected Signaling Pathways Of Iron Regulation In Hcc contrasting

confidence: 67%

Iron Deprivation Suppresses Hepatocellular Carcinoma Growth in Experimental Studies

Hao

Huang

et al. 2011

Clinical Cancer Research

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Purpose: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death, and iron overload is a significant risk factor in the development of HCC. In this study, we investigated the potential application of depriving iron by a novel iron chelator, thiosemicarbazone-24 (TSC24), in HCC treatment.Experimental Design: Two HCC cell lines and HFE knockout (HFE À/À ) mice were used to determine iron chelation efficiency of TSC24. The anticancer effects of TSC24 on HCC were analyzed in vitro and in athymic xenograft mouse models.Results: Treatment with TSC24 significantly decreased the cellular iron concentration in hepatoma cells and the serum iron concentration in HFE À/À mice by blocking iron uptake and interfering with normal regulation of iron levels. Moreover, the viability of HCC cell lines was reduced by TSC24. Confirming the mechanism of the agent, this decrease in viability could be partially rescued by addition of exogenous iron. TSC24 also suppressed tumor growth in athymic mice bearing human HCC xenografts in a concentration-dependent manner, without apparent toxicity in parallel with a decrease in the serum iron level. Further studies revealed that TSC24 efficiently triggered cell-cycle arrest and apoptosis in Hep3B and HepG2 cell lines. Conclusions: TSC24 is a potent iron chelator that suppresses human HCC tumor growth by disrupting iron homeostasis, reducing available iron, and triggering cell-cycle arrest and apoptosis, without apparent host toxicity at effective doses. Thus, TSC24 shows great potential for the treatment of HCC. Clin Cancer Res; 17(24); 7625-33. Ó2011 AACR.

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Section: Tsc24 Affected Signaling Pathways Of Iron Regulation In Hcc contrasting

confidence: 67%

Iron Deprivation Suppresses Hepatocellular Carcinoma Growth in Experimental Studies

Hao

Huang

et al. 2011

Clinical Cancer Research

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“…Interestingly, the combined radiation/SI113 therapy induced an almost complete de-phosphorylation of MDM2 on serine 166 that may indeed explain the enhanced sensitivity to radiation. SII13 treatment also altered the phosphorylation and the abundance of NDRG1, a protein that has been proposed as a potential clinical target for HCC [88], thus suggesting another possible mechanism through which the SI113-dependent SGK1-targeting might be beneficial in HCC treatment. The data obtained by a proteomic approach after treatment with SI113 are also extremely interesting for the definition of new cellular pathways dependent on SGK1 in HCC.…”

Section: Preclinical Model In Hcc: Effective Model For a Sgk1 Drug Tamentioning

confidence: 99%

SGK1, the New Player in the Game of Resistance: Chemo-Radio Molecular Target and Strategy for Inhibition

Talarico

Dattilo²,

D’Antona³

et al. 2016

Cell Physiol Biochem

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The serum- and glucocorticoid-regulated kinase (SGK) family consists of three members, SGK1, SGK2 and SGK3, all displaying serine/threonine kinase activity and sharing structural and functional similarities with the AKT family of kinases. SGK1 was originally described as a key enzyme in the hormonal regulation of several ion channels and pumps. Over time, growing and impressive evidence has been accumulated, linking SGK1 to the cell survival, de-differentiation, cell cycle control, regulation of caspases, response to chemical, mechanical and oxidative injury in cancer models as well as to the control of mitotic stability. Much evidence shows that SGK1 is over-expressed in a variety of epithelial tumors. More recently, many contributions to the published literature demonstrate that SGK1 can mediate chemo-and radio-resistance during the treatment of various human tumors, both in vitro and in vivo. SGK1 appears therefore as a dirty player in the stress response to chemical and radio-agents, responsible of a selective advantage that favors the uncontrolled tumor progression and the selection of the most aggressive clones. The purpose of this review is the analysis of the literature describing SGK1 as central node of the cell resistance, and a summary of the possible strategies in the pharmacological targeting of SGK1.

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“…In vitro, NDRG1 transcription was found decreased in colon cancer cell lines as well as breast and prostate cell lines compared with normal colon epithelium [3,12,19,20] . Studies reported that tumor cells with increased expression of NDRG1 exhibited lower metastatic potential [10,13] .…”

Section: Discussionmentioning

confidence: 99%

“…It exists in most tissues such as reproductive system, urinary system, digestive apparatus and immune system [1][2] , and exerts a number of functions, involved in cell growth [3] , cell cycle regulation [3] , P53-mediated apoptosis [4] , regulation of angiogenesis [5] , cell adhesion [6] , invasion [5] and metastasis [5,7] . Many studies have reported that NDRG1 is found to be downregulated in prostate cancer [8] , breast cancer [7] , colon cancer [9] and colorectal neoplasms [10][11] and overexpressed in hepatocellular carcinoma, cancers of the brain, skin, kidney and lung [12][13] . It was still shown that colon tumor cells with NDRG1 overexpression exhibited lower metastatic potential by using an invasion assay in vitro and metastases assay in vivo [13] , but colorectal cancer 18 cervical intraepithelial neoplasia (CIN Ⅱ-Ⅲ) and 63 cervical cancer tissues (including squamous cancer and adencarcinoma, diagnosed by pathological examination).…”

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confidence: 99%

Expression and biological function of N-myc down-regulated gene 1 in human cervical cancer

Wang

Cai

et al. 2010

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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The expression of N-myc down-regulated gene 1 (NDRG1) has previously been reported to be involved in the proliferation, differentiation, invasion and metastasis of cancer cells, but its role in cervical cancer is still unclear. This study aimed to investigate the expression of NDRG1gene in human cervical cancer and its effect on aggressive tumor behaviors. The NDRG1 expression in cervical tissues and cells was detected by RT-PCR. Specific expression plasmid pEGFP-N1-NDRG1-GFP was used to enhance the expression of NDRG1 in human cervical cancer cell lines. The mRNA and protein level of NDRG1 was assessed by RT-PCR and Western blotting, respectively. Its effects on cell proliferation, migration, invasion, cell cycle and apoptosis were detected by MTT, transwell migration assay and flow cytometry (FCM), respectively. The results showed that the expression of NDRG1 in cervical cancer tissues and cells was significantly lower than in normal cervical tissues (P<0.001). After transfection with pEGFP-N1-NDRG1-GFP, the mRNA and protein expression of NDRG1 was up-regulated in Siha cells, which suppressed cell proliferation (P<0.001), induced cell cycle arrest (P<0.05), reduced invasion and migration of Siha cells (P<0.05), but caused no cell apoptosis. Moreover, vascular endothelial growth factor (VEGF), a tumor-induced angiogenesis factor, was markedly reduced and E-cadherin, a cell adhesion molecule, was increased in the cells transfected with pEGFP-N1-NDRG1-GFP. It was concluded that up-regulated NDRG1 may play a role in the suppression of malignant cell growth, invasion and metastasis of human cervical cancer.

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N-Myc down-regulated gene 1 mediates proliferation, invasion, and apoptosis of hepatocellular carcinoma cells

Cited by 51 publications

References 25 publications

Iron Deprivation Suppresses Hepatocellular Carcinoma Growth in Experimental Studies

Iron Deprivation Suppresses Hepatocellular Carcinoma Growth in Experimental Studies

SGK1, the New Player in the Game of Resistance: Chemo-Radio Molecular Target and Strategy for Inhibition

Expression and biological function of N-myc down-regulated gene 1 in human cervical cancer

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