IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0035584.html
   My bibliography  Save this article

Factors Determining Sensitivity and Resistance of Tumor Cells to Arsenic Trioxide

Author

Listed:
  • Serkan Sertel
  • Margaret Tome
  • Margaret M Briehl
  • Judith Bauer
  • Kai Hock
  • Peter K Plinkert
  • Thomas Efferth

Abstract

Previously, arsenic trioxide showed impressive regression rates of acute promyelocytic leukemia. Here, we investigated molecular determinants of sensitivity and resistance of cell lines of different tumor types towards arsenic trioxide. Arsenic trioxide was the most cytotoxic compound among 8 arsenicals investigated in the NCI cell line panel. We correlated transcriptome-wide microarray-based mRNA expression to the IC50 values for arsenic trioxide by bioinformatic approaches (COMPARE and hierarchical cluster analyses, Ingenuity signaling pathway analysis). Among the identified pathways were signaling routes for p53, integrin-linked kinase, and actin cytoskeleton. Genes from these pathways significantly predicted cellular response to arsenic trioxide. Then, we analyzed whether classical drug resistance factors may also play a role for arsenic trioxide. Cell lines transfected with cDNAs for catalase, thioredoxin, or the anti-apoptotic bcl-2 gene were more resistant to arsenic trioxide than mock vector transfected cells. Multidrug-resistant cells overexpressing the MDR1, MRP1 or BCRP genes were not cross-resistant to arsenic trioxide. Our approach revealed that response of tumor cells towards arsenic trioxide is multi-factorial.

Suggested Citation

  • Serkan Sertel & Margaret Tome & Margaret M Briehl & Judith Bauer & Kai Hock & Peter K Plinkert & Thomas Efferth, 2012. "Factors Determining Sensitivity and Resistance of Tumor Cells to Arsenic Trioxide," PLOS ONE, Public Library of Science, vol. 7(5), pages 1-10, May.
    • Handle: RePEc:plo:pone00:0035584
    DOI: 10.1371/journal.pone.0035584
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035584
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0035584&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0035584?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0035584. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.