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Paclitaxel induced apoptosis in breast cancer cells requires cell cycle transit but not Cdc2 activity

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Abstract

Purpose

Paclitaxel (PTX) is a widely used chemotherapy agent and may cause cell death by apoptosis subsequent to microtubule (MT) disruption. In this paper, we have investigated whether cell cycle transit and or Cdc2 (Cdk1) activity is required for the apoptosis induced by PTX.

Methods

Cell cycle was analyzed by flow cytometry, Cdc2 was assayed bio chemically. Cdc2 activity was decreased by siRNA and dominant negative (dn) Cdc2 expression. Cells were arrested by chemical or biological inhibitors in a G1or S phase. Apoptosis was measured by DNA fragmentation and examination of nuclei by microscopy. JNK and AKT activations were assessed as well.

Results

Cell cycle inhibition was highly effective in decreasing PTX induced apoptosis. MT morphology was not altered by these inhibitors. PTX induced JNK activity or AKT mediated BAD phosphorylation was unaffected by cell cycle inhibitors. Abrogation of Cdc 2 activity was without effect on PTX induced apoptosis.

Conclusions

While cell cycle transit is required for PTX induced apoptosis; Cdc2 activity is not required.

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Abbreviations

Dn:

Dominant negative

MTs:

Microtubules

MTAs:

MT disrupting agents

m.o.i:

Multiplicity of infection

PTX:

Paclitaxel

p.f.u:

Plaque forming unit

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Acknowledgments

The authors acknowledge Amber Bible for editorial support and Richard Andrews for flow cytometry analyses. The study was supported by NIH (CA 84048).

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Authors and Affiliations

  1. Department of OB/GYN, GSM, UTMCK, University of Tennessee, Alcoa Highway, Knoxville, TN, 37920, USA

    D. Henley, M. Isbill, R. Fernando, J. S. Foster & J. Wimalasena

  2. Department of Pathobiology, University of Tennessee, Alcoa Highway, Knoxville, TN, 37920, USA

    J. Wimalasena

  3. Department of BCMB, Graduate School of Medicine, University of Tennessee, 1924 Alcoa Highway, Knoxville, TN, 37920, USA

    J. Wimalasena

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  1. D. Henley
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  2. M. Isbill
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Correspondence to J. Wimalasena.

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Henley, D., Isbill, M., Fernando, R. et al. Paclitaxel induced apoptosis in breast cancer cells requires cell cycle transit but not Cdc2 activity. Cancer Chemother Pharmacol 59, 235–249 (2007). https://doi.org/10.1007/s00280-006-0262-1

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  • DOI: https://doi.org/10.1007/s00280-006-0262-1

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