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

Psychoneuroendocrinology. 2009 Nov;34(10):1533-41. doi: 10.1016/j.psyneuen.2009.05.008. Epub 2009 Jun 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Aminopurine / analogs & derivatives
  • 2-Aminopurine / pharmacology
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • CDC2 Protein Kinase / antagonists & inhibitors
  • CDC2 Protein Kinase / physiology
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / physiology*
  • Epinephrine / pharmacology*
  • Female
  • Genomics / methods
  • Humans
  • Hydrocortisone / pharmacology*
  • Norepinephrine / pharmacology*
  • Paclitaxel / pharmacology*
  • Proteomics / methods
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • N(2)-(2-aminocyclohexyl)-N(6)-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine
  • 2-Aminopurine
  • CDC2 Protein Kinase
  • Paclitaxel
  • Hydrocortisone
  • Norepinephrine
  • Epinephrine