Growth delay of human pancreatic cancer cells by methylase inhibitor 5-aza-2′-deoxycytidine treatment is associated with activation of the interferon signalling pathway

Missiaglia, Edoardo; Donadelli, Massimo; Palmieri, Marta; Crnogorac‐Jurčević, Tatjana; Scarpa, Aldo; Lemoine, Nicholas R.

doi:10.1038/sj.onc.1208018

Cited by 78 publications

(67 citation statements)

References 79 publications

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“…Furthermore, 5-AzaC induced the activity of the interferon signaling pathway. 28 Together with our results, we infer that 5-AzaC may induce up-regulation of the genes related to stress response, for example, cytokines like interferon and interleukin.…”

Section: Discussionsupporting

confidence: 83%

Sequential gene expression changes in cancer cell lines after treatment with the demethylation agent 5‐Aza‐2′‐deoxycytidine

Arai

Yokosuka

Hirasawa

et al. 2006

Cancer

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Pristine‐, poly(octafluorotoluene)‐ (POFT), and polyacetylene (PAc)‐coated Si wafers were used as substrates for the study of segregation of silicone diacrylate (SA) from a formulation containing other oligomeric and monomeric acrylates. POFT and PAc were microwave plasma polymerized on the Si wafers. Three SAs with molecular weights ranging from 700 to 6000 Da were synthesized and characterized. Formulations with 2 wt % SA were ultraviolet cured on the silicon wafers. The surface composition of formulation‐substrate side of the cured film was analyzed with X‐ray photoelectron spectroscopy, and the depth profile was analyzed with time of flight‐secondary ion mass spectrometry. The analysis results indicated that SA aggregated on all three types of Si surfaces. However, SA segregation is highest on the low surface energy POFT‐coated Si substrate, and low‐molecular‐weight SA is favorable to the segregation. For high‐molecular‐weight SA, the different Si substrates do not affect the degree of aggregation at the formulation‐substrate interface. The observed SA aggregation trend can be predicted by the Gibbs‐adsorption equation correlated to the resin surface tension and contact angle on substrates. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 442–450, 2010

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Section: Discussionsupporting

confidence: 83%

Sequential gene expression changes in cancer cell lines after treatment with the demethylation agent 5‐Aza‐2′‐deoxycytidine

Arai

Yokosuka

Hirasawa

et al. 2006

Cancer

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“…Cyclin B1 is crucial for the transition from the G2 to the M phase. Aza induces G2/M arrest via the up-regulation of the p21 protein and the down-regulation of cyclin B1 mRNA in pancreatic cancer cells (33). In our study, p21 expression was moderately increased and cyclin B1 was decreased in the co-treatment group with Aza and VBL, compared to the control or VBL treatment alone groups.…”

Section: Discussionsupporting

confidence: 43%

A demethylating agent enhances chemosensitivity to vinblastine in a xenograft model of renal cell carcinoma

et al. 2011

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Abstract. Renal cell carcinoma (RCC) is resistant to chemotherapy partly due to the overexpression of the P-glycoprotein. Several tumor suppressor genes have been reported to be silenced by hypermethylation of the promoter region in RCC. We recently reported that the in vitro cytotoxicity of vinblastine (VBL) was enhanced by pre-treatment with the demethylating agent, 5-aza-2'-deoxycytidine (Aza), in the RCC cell line, Caki-1. In this study, we investigated the combined effect of Aza and VBL in a Caki-1 xenograft model and in other RCC cell lines in vitro. In the xenograft model, tumor volume and weight were significantly suppressed in the co-treatment group, compared to the control, and the expressions of P-glycoprotein, Bcl-2 and cyclin B1 were reduced. Thus, this combined effect could be mediated by the accumulation of intracellular VBL and the enhancement of apoptosis and cell cycle arrest. Moreover, the cytotoxicity of VBL was enhanced in vitro in three RCC cell lines by Aza treatment. These findings suggest that the combination treatment with Aza and VBL is effective against RCC.

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“…treatment of cancer cells with the methylase inhibitor, 5-aza-2 0 -deoxycytidine, has been shown to inhibit growth of cancer cells by activating interferon/STAT1-signaling pathways (Missiaglia et al, 2005). Thus, enhanced expression of SOCS1 or 5-aza-2 0 -deoxycytidine-induced growth suppression of breast-cancer cells noted in the study by Sutherland et al may well have derived from activation of STAT1, a transcription factor that is the primary inducer of SOCS1 (Hilton, 1999).…”

Section: Discussionmentioning

confidence: 99%

Expression of SOCS1 and SOCS3 genes is differentially regulated in breast cancer cells in response to proinflammatory cytokine and growth factor signals

Evans

Lohani

et al. 2006

Oncogene

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DNA-hypermethylation of SOCS genes in breast, ovarian, squamous cell and hepatocellular carcinoma has led to speculation that silencing of SOCS1 and SOCS3 genes might promote oncogenic transformation of epithelial tissues. To examine whether transcriptional silencing of SOCS genes is a common feature of human carcinoma, we have investigated regulation of SOCS genes expression by IFNc, IGF-1 and ionizing radiation, in a normal human mammary epithelial cell line (AG11134), two breastcancer cell lines (MCF-7, HCC1937) and three prostate cancer cell lines. Compared to normal breast cells, we observe a high level constitutive expression of SOCS2, SOCS3, SOCS5, SOCS6, SOCS7, CIS and/or SOCS1 genes in the human cancer cells. In MCF-7 and HCC1937 breast-cancer cells, transcription of SOCS1 is dramatically up-regulated by IFNc and/or ionizing-radiation while SOCS3 is transiently down-regulated by IFNc and IGF-1, suggesting that SOCS genes are not silenced in these cells by the epigenetic mechanism of DNAhypermethylation. We further show that the kinetics of SOCS1-mediated feedback inhibition of IFNc signaling is comparable to normal breast cells, indicating that the SOCS1 protein in breast-cancer cells is functional. We provide direct evidence that STAT3 pathways are constitutively activated in MCF-7 and HCC1937 cells and may drive the aberrant persistent activation of SOCS genes in breast-cancer cells. Our data therefore suggest that elevated expression of SOCS genes is a specific lesion of breast-cancer cells that may confer resistance to proinflammatory cytokines and trophic factors, by shutting down STAT1/STAT5 signaling that mediate essential functions in the mammary gland.

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Growth delay of human pancreatic cancer cells by methylase inhibitor 5-aza-2′-deoxycytidine treatment is associated with activation of the interferon signalling pathway

Cited by 78 publications

References 79 publications

Sequential gene expression changes in cancer cell lines after treatment with the demethylation agent 5‐Aza‐2′‐deoxycytidine

Sequential gene expression changes in cancer cell lines after treatment with the demethylation agent 5‐Aza‐2′‐deoxycytidine

A demethylating agent enhances chemosensitivity to vinblastine in a xenograft model of renal cell carcinoma

Expression of SOCS1 and SOCS3 genes is differentially regulated in breast cancer cells in response to proinflammatory cytokine and growth factor signals

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