Dataset Information

Proteomic profile of oxaliplatin treated cell line reveals DNA damage induced nucleolar stress as main response.Proteomic profile of oxaliplatin treated cell line reveals DNA damage induced nucleolar stress as main response

ABSTRACT: Oxaliplatin is a widely used anti-cancer drug. It is part of treatment regimens for colorectal and pancreatic cancers, but it is tested in esophageal, biliary tract, gastric or hepatocellular cancers as well. Contrary to this wide application, there is only limited amount of information about oxaliplatin mechanism and response to treatment. We have performed whole-cell proteomic study to obtain cellular response induced by oxaliplatin. For this purpose we have treated CCRF-CEM cell line by 5xIC50 (29.3 μM) for half-time to caspase activation (240 min). The complex proteomic comparison was done on the treated vs. un-treated cells by high-resolution mass spectrometry. We have identified 4049 proteins in average from three biological replicates. From such pool just 76 proteins were significantly downregulated and 31 proteins upregulated in at least of two replicates. Both upregulated and dowregulated proteins are involved in DNA damage response, which is the most significant effect of platinum drugs. Downregulated proteins are split into three fractions. One fraction was centrosomal proteins or proteins involved in G2/M regulation. Second fraction was RNA processing proteins or proteins of processome of both ribosomal subunits. Downregulation of those proteins shows to ongoing nucleolar stress. Third fraction consisted of several ribosomal proteins. This should be sign of ribosomal stress. Nucleolar and ribosomal stress are stress responses manifesting by nucleolar shrinkage or and by inhibition of ribosomal biogenesis. Cellular response to oxaliplatin is thus DNA damage response, which triggers nucleolar and subsequent ribosomal stress.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Suspension Culture, T Cell

SUBMITTER: Tomáš Oždian

LAB HEAD: Marián Hajdúch

PROVIDER: PXD003543 | Pride | 2017-05-11

REPOSITORIES: Pride

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			Action	DRS
	OxaPt_5xIC50_080408_01.raw	Raw
	OxaPt_5xIC50_080408_02.raw	Raw
	OxaPt_5xIC50_080408_03.raw	Raw
	OxaPt_5xIC50_080408_04.raw	Raw
	OxaPt_5xIC50_080408_05.raw	Raw

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Proteomic profiling reveals DNA damage, nucleolar and ribosomal stress are the main responses to oxaliplatin treatment in cancer cells.

Ozdian Tomas T Holub Dusan D Maceckova Zuzana Z Varanasi Lakshman L Rylova Gabriela G Rehulka Jiri J Vaclavkova Jana J Slavik Hanus H Moudry Pavel P Znojek Pawel P Stankova Jarmila J de Sanctis Juan Bautista JB Hajduch Marian M Dzubak Petr P

Journal of proteomics 20170503

Oxaliplatin is widely used to treat colorectal cancer in both palliative and adjuvant settings. It is also being tested for use in treating hematological, esophageal, biliary tract, pancreatic, gastric, and hepatocellular cancers. Despite its routine clinical use, little is known about the responses it induces in cancer cells. Therefore the whole-cell proteomics study was conducted to characterize the cellular response induced by oxaliplatin. Chemosensitive CCRF-CEM cells were treated with oxali ...[more]

PMID: 28478306

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