Nanomolar range docetaxel treatment sensitizes MCF-7 cells to chemotherapy induced apoptosis, induces G2M arrest and phosphorylates bcl-2*

Guy J. Berchem*, Manon Bosseler, Natacha Mine, Bernard Avalosse

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

52 Citations (Scopus)

Abstract

Docetaxel (Taxotere(TM)), a member of the taxoid family of chemotherapy drugs is currently being tested in clinical trials simultaneously with other apoptosis inducing drugs like doxorubicin. We show, in vitro, in MCF-7 breast cancer cells that when it is used at doses as low as 5 nM, 24 hours before either doxorubicin or etoposide, docetaxel is capable of inducing a significant increase in cell death compared to the reverse sequence or simultaneous treatment. We further show that this increase in cell death is due to an increase in apoptosis, and that this sensitization coincides with a docetaxel induced G2-M arrest and phosphorylation of the bcl-2 oncoprotein. We speculate that this phosphorylation of the apoptosis blocker bcl-2 might be responsible for the sensitization, and we suggest a clinical study comparing a 24 hour docetaxel pretreatment to the current simultaneous schedules.

Original languageEnglish
Pages (from-to)535-540
Number of pages6
JournalAnticancer Research
Volume19
Issue number1 A
Publication statusPublished - 1999
Externally publishedYes

Keywords

  • Breast cancer
  • Cell cycle
  • Doxorubicin
  • Etoposide
  • Programmed cell death

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