title: Doxorubicin Affects Expression of Proteins of Neuronal Pathways in MCF-7 Breast Cancer Cells.
abstract: In the present article, we report on the semi-quantitative proteome analysis and related changes in protein expression of the MCF-7 breast cancer cell line following treatment with doxorubicin, using the precursor acquisition independent from ion count (PAcIFIC) mass spectrometry method. PAcIFIC represents a cost-effective and easy-to-use proteomics approach, enabling for deep proteome sequencing with minimal sample handling. The acquired proteomic data sets were searched for regulated Reactome pathways and Gene Ontology annotation terms using a new algorithm (SetRank). Using this approach, we identified pathways with significant changes (≤0.05), such as chromatin organization, DNA binding, embryo development, condensed chromosome, sequence-specific DNA binding, response to oxidative stress and response to toxin, as well as others. These sets of pathways are already well-described as being susceptible to chemotherapeutic drugs. Additionally, we found pathways related to neuron development, such as central nervous system neuron differentiation, neuron projection membrane and SNAP receptor activity. These later pathways might indicate biological mechanisms on the molecular level causing the known side-effect of doxorubicin chemotherapy, characterized as cognitive impairment, also called 'chemo brain'. Mass spectrometry data are available via ProteomeXchange with identifier PXD002998.
authors.affiliation: Department of Medical and Clinical Biophysics, Faculty of Medicine, University of Pavol Jozef Safarik, Kosice, Slovak Republic Department of Clinical Research, Proteomics and Mass Spectrometry Core Facility, University of Bern, Bern, Switzerland.
authors.forename: Marian
authors.initials: M
authors.lastname: Petrovic
authors.affiliation: Department of Clinical Research, Proteomics and Mass Spectrometry Core Facility, University of Bern, Bern, Switzerland.
authors.forename: Cedric
authors.initials: C
authors.lastname: Simillion
authors.affiliation: International Clinical Research Center, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Kruzliak
authors.affiliation: Department of Medical and Clinical Biophysics, Faculty of Medicine, University of Pavol Jozef Safarik, Kosice, Slovak Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Sabo
authors.affiliation: Department of Clinical Research, Proteomics and Mass Spectrometry Core Facility, University of Bern, Bern, Switzerland manfred.heller@dkf.unibe.ch.
authors.forename: Manfred
authors.initials: M
authors.lastname: Heller
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry; D001921:Brain / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism*; D002454:Cell Differentiation; D004317:Doxorubicin / Q000009:adverse effects / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D013058:Mass Spectrometry; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress; D020543:Proteome / Q000378:metabolism; D040901:Proteomics
chemical_list: D000970:Antineoplastic Agents; D020543:Proteome; D004317:Doxorubicin
keywords: Doxorubicin; LC-MS/MS; PAcIFIC; breast cancer; chemo brain; chemotherapy; neuronal pathway down-regulation; pathway analysis; side-effects