2-methoxyestradiol sensitizes breast cancer cells to taxanes by targeting centrosomes

Randa El-Zein, Jose Thaiparambil, Sherif Z. Abdel-Rahman

Research output: Contribution to journalArticlepeer-review

Abstract

Centrosomes amplification is a hallmark of cancer. We hypothesize that 2-methoxyestradiol (2-ME) sensitizes breast cancer (BC) cells to taxanes by targeting amplified centrosomes. We assessed the extent by which 2-ME together with paclitaxel (PTX) induces centrosome alterations with subsequent mitotic catastrophe in different BC subtypes. 2-ME induced a significant reduction in PTX IC50 values in all cells tested ranging from 28-44% (P < 0.05). Treatment with both PTX and 2-ME significantly increased the number of misaligned metaphases compared to PTX alone (34%, 100% and 52% for MCF7, MDA-MB231 and SUM149, respectively; P < 0.05). The number of cells with multipolar spindle formation was significantly increased (81%, 220% and 285% for MCF7, MDA-MB231 and SUM 149, respectively; P < 0.05). PTX and 2-ME treatment significantly increased interphase declustering in cancer cells (56% for MCF7, 208% for MDA-MB231 and 218% for SUM149, respectively; P < 0.05) and metaphase declustering (1.4-fold, 1.56-fold and 2.48-fold increase for MCF7, MDAMB231 and SUM149, respectively; P < 0.05). This report is the first to document centrosome declustering as a mechanism of action of 2-ME and provides a potential approach for reducing taxane toxicity in cancer treated patients.

Original languageEnglish (US)
Pages (from-to)4479-4489
Number of pages11
JournalOncotarget
Volume11
Issue number48
DOIs
StatePublished - 2020

Keywords

  • 2-methoxyestradiol (2-ME)
  • Breast cancer
  • Centrosome amplification
  • Centrosome declustering

ASJC Scopus subject areas

  • Oncology

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