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

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

Author information

1
Department of Pharmacology & Chemical Biology, Pittsburgh, PA 15213, United States. flintms@upmc.edu

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.

PMID:
19560278
DOI:
10.1016/j.psyneuen.2009.05.008
[Indexed for MEDLINE]

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