Contribution of reactive oxygen species and caspase-3 to apoptosis and attenuated ICAM-1 expression by paclitaxel-treated MDA-MB-435 breast carcinoma cells

  • Authors:
    • Helen Fawcett
    • Jamie S. Mader
    • Matthew Robichaud
    • Carman Giacomantonio
    • David W. Hoskin
  • View Affiliations

  • Published online on: December 1, 2005     https://doi.org/10.3892/ijo.27.6.1717
  • Pages: 1717-1726
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Abstract

Paclitaxel is a microtubule-stabilizing and apoptosis-inducing drug that is commonly used to treat metastatic breast cancer, although the mechanism of paclitaxel-induced apoptosis remains incompletely understood. Furthermore, adhesion molecule expression is attenuated on mouse mastocytoma and human leukemia cells that survive short-term culture in the presence of paclitaxel. In the present study we show that MDA-MB-435 human breast carcinoma cells that survived culture for 72 h in the presence of submaximal cytotoxic concentrations of paclitaxel (0.02 and 0.01 µg/ml) showed decreased expression of the adhesion molecule ICAM-1. Paclitaxel treatment of MDA-MB-435 cells was associated with the generation of reactive oxygen species (ROS), dissipation of mitochondrial transmembrane potential, and the activation of caspase-3. The antioxidant glutathione protected MDA-MB-435 cells from paclitaxel-induced cytotoxicity and reduced ICAM-1 expression. In addition, a selective inhibitor of caspase-3 (Z-DEVD-FMK), as well as a pan-caspase inhibitor (Z-VAD-FMK), partially prevented the decrease in ICAM-1 expression observed following paclitaxel treatment, but did not protect against paclitaxel-induced cytotoxicity. We conclude that the paclitaxel-induced reduction in ICAM-1 expression by MDA-MB-435 breast carcinoma cells is both ROS- and caspase-dependent, whereas paclitaxel-induced cytotoxicity is ROS-dependent and does not involve caspases. Decreased ICAM-1 expression by breast carcinoma cells that survive paclitaxel treatment may negatively impact on cytotoxic lymphocyte-mediated destruction of paclitaxel-resistant breast cancer cells in the context of chemo-immunotherapy or chemo-adoptive immunotherapy.

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December 2005
Volume 27 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Fawcett, H., Mader, J.S., Robichaud, M., Giacomantonio, C., & Hoskin, D.W. (2005). Contribution of reactive oxygen species and caspase-3 to apoptosis and attenuated ICAM-1 expression by paclitaxel-treated MDA-MB-435 breast carcinoma cells. International Journal of Oncology, 27, 1717-1726. https://doi.org/10.3892/ijo.27.6.1717
MLA
Fawcett, H., Mader, J. S., Robichaud, M., Giacomantonio, C., Hoskin, D. W."Contribution of reactive oxygen species and caspase-3 to apoptosis and attenuated ICAM-1 expression by paclitaxel-treated MDA-MB-435 breast carcinoma cells". International Journal of Oncology 27.6 (2005): 1717-1726.
Chicago
Fawcett, H., Mader, J. S., Robichaud, M., Giacomantonio, C., Hoskin, D. W."Contribution of reactive oxygen species and caspase-3 to apoptosis and attenuated ICAM-1 expression by paclitaxel-treated MDA-MB-435 breast carcinoma cells". International Journal of Oncology 27, no. 6 (2005): 1717-1726. https://doi.org/10.3892/ijo.27.6.1717