Global gene expression analysis in time series following N-acetyl L-cysteine induced epithelial differentiation of human normal and cancer cells in vitro

Gustafsson, Anna; Kupershmidt, Ilya; Edlundh-Rose, Esther; Greco, Giulia; Serafino, Annalucia; Krasnowska, Ewa K.; Lundeberg, Thomas; Bracci-Laudiero, Luisa; Romano, Maria-Concetta; Parasassi, Tiziana; Lundeberg, Joakim

doi:10.1186/1471-2407-5-75

Cited by 40 publications

(31 citation statements)

References 70 publications

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“…However, recent work from our laboratory and those of the others established other important functions for NAC which could be the basis for its death inhibitory property [12,13]. Here we demonstrate that the basis for cell death inhibitory function of NAC could be its capacity to induce NFκB, and modulate important differentiation and activation genes in DPSCs.…”

Section: Discussionsupporting

confidence: 54%

“…[12,13]. In contrast, significant increases in the cell proliferation and cell numbers was seen when NAC was added to untreated and HEMA treated cells when compared to HEMA alone treated cells.…”

Section: Discussionmentioning

confidence: 90%

“…NAC is shown to be the precursor of glutathiones (GSH) with a significant antioxidant effect. Although previously published reports on the function of NAC have largely been concentrated on its anti-oxidant effect, recent reports have underscored the significance of this compound in inhibition of proliferation and induction of differentiation [12][13][14]. NAC has also been regarded as an anti-inflammatory compound [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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N-acetylcysteine protects dental pulp stromal cells from HEMA-induced apoptosis by inducing differentiation of the cells

Paranjpe

Cacalano

Hume

et al. 2007

Free Radical Biology and Medicine

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Resin based materials are now widely used in dental restorations. While the use of these materials is aesthetically appealing in patients, they carry the risk of local and systemic adverse effects. The potential risks are direct damage to the cells and induction of immune-based hypersensitivity reactions. Dental Pulp Stromal Cells (DPSCs) and oral keratinocytes are the major cell types which may come in contact with dental resins such as 2-hydroxyethyl methacrylate (HEMA) after dental restorations. Here we show that N-acetyl cysteine (NAC) inhibits HEMA induced apoptotic cell death and restores the function of DPSCs and oral epithelial cells. NAC inhibits HEMA mediated toxicity through induction of differentiation in DPSCs since the genes for dentin sialoprotein (DSP), Osteopontin (OPN), Osteocalcin (OCN), and Alkaline Phosphatase (ALP) which are induced during differentiation are also induced by NAC. Unlike NAC, Vitamin E and C which known anti-oxidant compounds failed to prevent either HEMA mediated cell death or decrease in VEGF secretion by human DPSCs. More importantly, when added either alone or in combination with HEMA Vitamin E and Vitamin C did not increase the gene expression for OPN, and in addition Vitamin E inhibited the protective effect of NAC on DPSCs. NAC inhibited HEMA mediated decrease in NFκB activity thus, providing survival mechanism for the cells. Overall, the studies reported in this paper indicated that undifferentiated DPSCs have exquisite sensitivity to HEMA induced cell death, and their differentiation by NAC resulted in an increased NFκB activity which might have provided the basis for their increased protection from HEMA mediated functional loss and cell death.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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N-acetylcysteine protects dental pulp stromal cells from HEMA-induced apoptosis by inducing differentiation of the cells

Paranjpe

Cacalano

Hume

et al. 2007

Free Radical Biology and Medicine

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“…Three days after NAC exposure, differentiation of NHEK is demonstrated by an increased number of intracellular junctions, basal localization of actin as well as by ceased proliferation [4] . These observations could also be confi rmed by an Affymetrix gene expression analysis encompassing 12,000 gene sequences [5] .…”

Section: Introductionmentioning

confidence: 65%

“…Previous morphological and biochemical studies have indicated that NHEK, as well as the colon carcinoma cell line Caco-2, undergo an accelerated differentiation upon treatment with NAC [4,5] . In fi gure 1 , we show that NAC treatment induces cytoskeletal remodelling and formation of adherens junctions in NHEK, indicating a reversion from a proliferation state to differentiation, without affecting cell viability.…”

Section: Experimental Overviewmentioning

confidence: 99%

Gene Expression Analysis of Human Epidermal Keratinocytes after N-Acetyl <i>L</i>-Cysteine Treatment Demonstrates Cell Cycle Arrest and Increased Differentiation

et al. 2005

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Objectives: Several cancer prevention programmes have previously been executed using treatment of antioxidant compounds. The antioxidant N-acetyl L-cysteine (NAC), a membrane-permeable aminothiol, is a sulfhydryl reductant reducing oxidised glutathione, as well as being a precursor of intracellular cysteine and glutathione. A previous report based on the cellular response to NAC treatment showed that NAC induced a 10-fold more rapid differentiation in normal primary keratinocytes as well as a reversion of a colon carcinoma cell line from neoplastic proliferation to apical-basolateral differentiation. In order to investigate molecular events underlying thechanges in proliferation and differentiation induced by NAC treatment, we performed global gene expression analysis of normal human epidermal keratinocytes in a time series. Methods: Treated samples were compared to untreated samples through a reference design using a spotted cDNA array comprising approximately 30,000 features. B statistics was used to identify differentially expressed genes, and RT-PCR of a selected set of genes was performed to verify differential expression. Results: The number of differentially expressed genes increased over time, starting with 0 at 30 min, 73 at 3 h and increasing to 952 genes at 48 h. Results of the expression analysis showed arrest of the cell cycle and an upregulation of cytoskeletal reorganisation, implicating increased differentiation. A comparison to gene ontology groups indicated downregulation of a large number of genes involved in cell proliferation and regulation of the cell cycle. Conclusions: A significant fraction of the differentially expressed genes could be classified according to their role in the differentiation process, demonstrating that NAC regulates the conversion from proliferation to differentiation at a transcriptional level.

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Interfering with Smoking‐Induced Pathophysiology

Csordás

2011

Cigarette Smoke Toxicity

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Global gene expression analysis in time series following N-acetyl L-cysteine induced epithelial differentiation of human normal and cancer cells in vitro

Cited by 40 publications

References 70 publications

N-acetylcysteine protects dental pulp stromal cells from HEMA-induced apoptosis by inducing differentiation of the cells

N-acetylcysteine protects dental pulp stromal cells from HEMA-induced apoptosis by inducing differentiation of the cells

Gene Expression Analysis of Human Epidermal Keratinocytes after N-Acetyl <i>L</i>-Cysteine Treatment Demonstrates Cell Cycle Arrest and Increased Differentiation

Interfering with Smoking‐Induced Pathophysiology

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