Proteomic analysis of the vitamin C effect on the doxorubicin cytotoxicity in the MCF-7 breast cancer cell line

P. Bober, M. Alexovic, I. Talian, Z. Tomkova, Z. Viscorova, M. Benckova, I. Andrasina, R. Ciccocioppo, D. Petrovic, M. Adamek, P. Kruzliak, J. Sabo

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: Doxorubicin is an anthracycline drug which inhibits the growth of breast cancer cell lines. However, a major factor limiting its use is a cumulative, dose-dependent cardiotoxicity, resulting in a permanent loss of cardiomyocytes. Vitamin C was found to potentiate the cytotoxic effects of a variety of chemotherapeutic drugs including doxorubicin. The aim javascript:void(0);of the study was to describe the changes in protein expression and proliferation of the MCF-7 cells induced by the vitamin C applied with doxorubicin. METHODS: Label-free quantitative proteomics and real-time cell analysis methods were used to search for proteome and cell proliferation changes. These changes were induced by the pure DOX and by DOX combined with vitamin C applied on the MCF-7 cell line. RESULTS: From the real-time cell analysis experiments, it is clear that the highest anti-proliferative effect occurs with the addition of 200 microM of vitamin C to 1 microM of doxorubicin. By applying both the label-free protein quantification method and total ion current assay, we found statistically significant changes (p </= 0.05) of 26 proteins induced by the addition of vitamin C to doxorubicin on the MCF-7 cell line. These differentially expressed proteins are involved in processes such as structural molecule activity, transcription and translation, immune system process and antioxidant, cellular signalling and transport. CONCLUSION: The detected proteins may be capable of predicting response to DOX therapy. This is a key tool in the treatment of breast cancer, and the combination with vit C seems to be of particular interest due to the fact that it can potentiate anti-proliferative effect of DOX.
Original languageEnglish
Pages (from-to)35-42
Number of pages8
JournalJournal of Cancer Research and Clinical Oncology
Volume143
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • Antibiotics, Antineoplastic/pharmacology
  • Antioxidants/pharmacology
  • Ascorbic Acid/pharmacology
  • Breast Neoplasms/drug therapy/metabolism
  • Cell Proliferation
  • Doxorubicin/pharmacology
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Female
  • Humans
  • MCF-7 Cells
  • Proteome/metabolism
  • Proteomics
  • Cell toxicity
  • Doxorubicin
  • Label-free quantification
  • MCF-7 cell line
  • Vitamin C

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