Stress hormones mediate drug resistance to paclitaxel in human breast cancer cells through a CDK-1-dependent pathway

Melanie S. Flint*, Grace Kim, Brian L. Hood, Nicholas W. Bateman, Nicolas A. Stewart, Thomas P. Conrads

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Chemotherapy comprises part of successful treatment regimens for breast cancer, however, up to 50% of patients develop resistance. Stress in cancer patients can equate to poor chemotherapeutic responses. We hypothesize that drug resistance may be associated with stress hormone-induced alterations in breast cancer cells. To test this hypothesis, MDA-MB-231 cells were cultured with paclitaxel and/or cortisol, norepinephrine and epinephrine and cytotoxicity, cell cycle analyses, genomic and proteomic analyses were performed. Paclitaxel-mediated cytotoxicity and G2/M cell cycle arrest were reversed significantly by stress hormones. Genomic and proteomic analyses revealed that stress hormones modulated beta-tubulin isotypes and significantly altered genes and proteins involved in regulation of the G2/M transition, including cyclin-dependent kinase-1 (CDK-1). Inhibition of CDK-1 abrogated stress hormone-mediated reversal of paclitaxel-induced cytotoxicity, indicating that the protective effect of stress hormones act through a CDK-1-dependent mechanism. These data demonstrate that stress hormones interfere with paclitaxel efficacy and contribute significantly to drug resistance.

Original languageEnglish
Pages (from-to)1533-1541
Number of pages9
JournalPsychoneuroendocrinology
Volume34
Issue number10
DOIs
StatePublished - Nov 2009

Keywords

  • Breast cancer
  • Cortisol
  • Epinephrine
  • Paclitaxel
  • Stress

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