Dataset Information

Proteome expression changes upon Halofuginone treatment

ABSTRACT: NHCF-V primary cardiac fibroblasts where treated for 24 hours with either 1) 100nM Halofuginone (TMT labels 126 and 129L) 2) 300nM Halofuginone (TMT labels 127L and 129H) 3) 300 nM Halofuginone + 4 mM L-Pro (TMT labels 127H and 130L) 4) DMSO (TMT labels 128H and 131)

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Primary Cell, Fibroblast

SUBMITTER: Maria Faelth Savitski

LAB HEAD: Marcus Bantscheff

PROVIDER: PXD005679 | Pride | 2017-05-16

REPOSITORIES: Pride

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Publications

Activation of the Amino Acid Response Pathway Blunts the Effects of Cardiac Stress.

Qin Pu P Arabacilar Pelin P Bernard Roberta E RE Bao Weike W Olzinski Alan R AR Guo Yuanjun Y Lal Hind H Eisennagel Stephen H SH Platchek Michael C MC Xie Wensheng W Del Rosario Julius J Nayal Mohamad M Lu Quinn Q Roethke Theresa T Schnackenberg Christine G CG Wright Fe F Quaile Michael P MP Halsey Wendy S WS Hughes Ashley M AM Sathe Ganesh M GM Livi George P GP Kirkpatrick Robert B RB Qu Xiaoyan A XA Rajpal Deepak K DK Faelth Savitski Maria M Bantscheff Marcus M Joberty Gerard G Bergamini Giovanna G Force Thomas L TL Gatto Gregory J GJ Hu Erding E Willette Robert N RN

Journal of the American Heart Association 20170509 5

<h4>Background</h4>The amino acid response (AAR) is an evolutionarily conserved protective mechanism activated by amino acid deficiency through a key kinase, general control nonderepressible 2. In addition to mobilizing amino acids, the AAR broadly affects gene and protein expression in a variety of pathways and elicits antifibrotic, autophagic, and anti-inflammatory activities. However, little is known regarding its role in cardiac stress. Our aim was to investigate the effects of halofuginone, ...[more]

PMID: 28487390

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Project description:Reversal of gene promoter DNA hypermethylation and associated abnormal gene silencing is an attractive approach to cancer therapy. The DNA methylation inhibitor, decitabine (5-aza-2'-deoxycitidine), is proving efficacious for hematological neoplasms especially at lower, less toxic, doses. Experimentally, high doses induce rapid DNA damage and cytotoxicity, but these may not explain the prolonged time to response seen in patients. Transient exposure of leukemic and solid tumor cells to clinically-relevant nanomolar doses, without causing immediate cytotoxicity or apoptosis, produces sustained reduced tumorigenicity, and for leukemia cells, diminished long-term self-renewal. These effects appear triggered by cellular reprogramming and include sustained decreases in promoter DNA methylation with associated gene re-expression, and anti-tumor changes in multiple key cellular regulatory pathways, most of which are high priority targets for pharmacologic anti-cancer strategies. Thus, low dose decitabine regimens appear to have broad applicability for cancer management. [Gene expression profiling] Leukemia cell lines Kasumi-1 and KG1A are treated with 10nM DAC during 72 hours and gene expression was assayed at day 3, 7 and 14 after the start of the treatment. Appropriate mock treated samples were used as control in each case. In addition, Kasumi-1 cells were also treated with a higher dose of DAC (500nM), 100nM ARA-C and 300 nM TSA, again controlled against mock treated Kasumi-1 cells, to separate dose and agent dependent effects. MCF7 was studied as an example of a solid tumor cell line. Therefore MCF7 cells were treated with 100nM DAC and results were assayed at day 1, day 3 and day 10. [Methylation profiling] The effects of the demethylating agent DAC were studied in the leukemia cell line Kasumi-1 over a 28 day time course. Intermediate time points were studied at days 3, 7, 14 and 21. These results were verfied in KG1A and KG1 leukemia cell lines, at one selected time point. The effects on one primary sample were also studied. Four normal leukemia samples (PL1, 2, 4 and 5) were used as general controls. The effect of DAC was compared to ARA-C, TSA. Both mock treated and day 3 DAC treated Kasumi-1 cells were repeated. These results were verified at one selected time point for the DAC treated MCF7 breast cancer cell line.

Dataset Information

Proteome expression changes upon Halofuginone treatment

Publications

Activation of the Amino Acid Response Pathway Blunts the Effects of Cardiac Stress.

Similar Datasets

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