Telling Cells How to Die: Docetaxel Therapy in Cancer Cell Lines

Taxanes (paclitaxel and docetaxel) are antimicrotubule agents used in the clinical practice for the treatment of solid tumors. The molecular mechanisms of taxane-dependent cytotoxicity are only partially known. In vitro, different modes of action have been established for paclitaxel according to its concentration. A similar phenomenon has been shown for other microtubule-stabilizing drugs, including docetaxel. Recently, we described two different forms of mitotic exit in breast cancer cell lines exposed to docetaxel. The causes and consequences of the dual mechanism of cytotoxicity of this agent are discussed here.

[1]  J. Pietenpol,et al.  Defective G1-S cell cycle checkpoint function sensitizes cells to microtubule inhibitor-induced apoptosis. , 1999, Cancer research.

[2]  T. Motyl,et al.  Autophagy is the dominant type of programmed cell death in breast cancer MCF-7 cells exposed to AGS 115 and EFDAC, new sesquiterpene analogs of paclitaxel , 2005, Anti-cancer drugs.

[3]  Tomohiro Matsumoto,et al.  Low Concentrations of Taxol Cause Mitotic Delay Followed by Premature Dissociation of p55CDC from Mad2 and BubR1 and Abrogation of the Spindle checkpoint, Leading to Aneuploidy , 2005, Cell cycle.

[4]  Robert J. Gillies,et al.  Docetaxel induces cell death through mitotic catastrophe in human breast cancer cells , 2005, Molecular Cancer Therapeutics.

[5]  B. Weaver,et al.  Decoding the links between mitosis, cancer, and chemotherapy: The mitotic checkpoint, adaptation, and cell death. , 2005, Cancer cell.

[6]  Geert J. P. L. Kops,et al.  On the road to cancer: aneuploidy and the mitotic checkpoint , 2005, Nature Reviews Cancer.

[7]  S. Kaufmann,et al.  A multistep model for paclitaxel-induced apoptosis in human breast cancer cell lines. , 2001, Experimental cell research.

[8]  V. Boudný,et al.  Src tyrosine kinase augments taxotere-induced apoptosis through enhanced expression and phosphorylation of Bcl-2 , 2002, British Journal of Cancer.

[9]  Weikang Tao.  The Mitotic Checkpoint in Cancer Therapy , 2005, Cell cycle.

[10]  S. Horwitz,et al.  Mechanisms of Taxol-induced cell death are concentration dependent. , 1998, Cancer research.

[11]  L. Neckers,et al.  Taxol-induced apoptosis and phosphorylation of Bcl-2 protein involves c-Raf-1 and represents a novel c-Raf-1 signal transduction pathway. , 1996, Cancer research.

[12]  T. Fojo,et al.  Histone deacetylase inhibitors all induce p21 but differentially cause tubulin acetylation, mitotic arrest, and cytotoxicity. , 2002, Molecular cancer therapeutics.

[13]  M. Jordan,et al.  Microtubules as a target for anticancer drugs , 2004, Nature Reviews Cancer.

[14]  E. Perez,et al.  Weekly administration of docetaxel and paclitaxel in metastatic or advanced breast cancer. , 2005, The oncologist.

[15]  Qin Wang,et al.  All-trans retinoic acid potentiates Taxotere-induced cell death mediated by Jun N-terminal kinase in breast cancer cells , 2004, Oncogene.

[16]  W. Priebe,et al.  Mitotic Catastrophe Results in Cell Death by Caspase-Dependentand Caspase-Independent Mechanisms , 2006, Cell cycle.

[17]  M. Cammer,et al.  Gene expression and mitotic exit induced by microtubule-stabilizing drugs. , 2003, Cancer research.

[18]  T. Fojo,et al.  Low concentrations of paclitaxel induce cell type-dependent p53, p21 and G1/G2 arrest instead of mitotic arrest: molecular determinants of paclitaxel-induced cytotoxicity , 2001, Oncogene.

[19]  C. Croce,et al.  Bcl2 is the guardian of microtubule integrity. , 1997, Cancer research.

[20]  S. Fesik,et al.  Human Chk1 expression is dispensable for somatic cell death and critical for sustaining G2 DNA damage checkpoint. , 2003, Molecular cancer therapeutics.

[21]  I. Roninson,et al.  If not apoptosis, then what? Treatment-induced senescence and mitotic catastrophe in tumor cells. , 2001, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[22]  G. Moreno-Bueno,et al.  Molecular profiling of docetaxel cytotoxicity in breast cancer cells: uncoupling of aberrant mitosis and apoptosis , 2007, Oncogene.

[23]  G. Giaccone,et al.  Paclitaxel triggers cell death primarily via caspase-independent routes in the non-small cell lung cancer cell line NCI-H460. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[24]  Z. Zong,et al.  Lack of synchrony among multiple nuclei induces partial DNA fragmentation in V79 cells polyploidized by demecolcine , 1999, Cell proliferation.

[25]  M. Bornens,et al.  Pulse treatment of interphasic HeLa cells with nanomolar doses of docetaxel affects centrosome organization and leads to catastrophic exit of mitosis. , 1997, Journal of cell science.

[26]  E. Gabrielson,et al.  Variable levels of chromosomal instability and mitotic spindle checkpoint defects in breast cancer. , 2002, The American journal of pathology.

[27]  M. Blagosklonny.  Prolonged Mitosis Versus Tetraploid Checkpoint: How p53 Measures the Duration of Mitosis , 2006, Cell cycle.

[28]  G. Berchem,et al.  Nanomolar range docetaxel treatment sensitizes MCF-7 cells to chemotherapy induced apoptosis, induces G2M arrest and phosphorylates bcl-2. , 1999, Anticancer research.

[29]  V. Baldin,et al.  Involvement of p21 in mitotic exit after paclitaxel treatment in MCF-7 breast adenocarcinoma cell line , 1997, Oncogene.

[30]  I. Roninson,et al.  p21Waf1/Cip1/Sdi1-induced growth arrest is associated with depletion of mitosis-control proteins and leads to abnormal mitosis and endoreduplication in recovering cells , 2000, Oncogene.

[31]  M. Marra,et al.  Docetaxel induces p53-dependent apoptosis and synergizes with farnesyl transferase inhibitor r115777 in human epithelial cancer cells. , 2005, Frontiers in bioscience : a journal and virtual library.

[32]  M. Debatisse,et al.  Sustained mitotic block elicits DNA breaks: one-step alteration of ploidy and chromosome integrity in mammalian cells , 2007, Oncogene.

[33]  M. Kirschner,et al.  Dynamic instability of microtubule growth , 1984, Nature.

[34]  G. Hortobagyi,et al.  Docetaxel for treatment of solid tumours: a systematic review of clinical data. , 2005, The Lancet. Oncology.