Reconstitution of caspase-3 sensitizes MCF-7 breast cancer cells to radiation therapy

  • Authors:
    • Xiao He Yang
    • Susan Edgerton
    • Ann D. Thor
  • View Affiliations

  • Published online on: June 1, 2005     https://doi.org/10.3892/ijo.26.6.1675
  • Pages: 1675-1680
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Abstract

Caspase-3 plays an important role in apoptotic execution. Caspase-3 deficiency or down-regulation has been reported in breast and other kinds of cancers. Given the redundancy of caspase cascade, however, the impact of caspase-3 deficiency/down-regulation on radiation-induced apoptosis remains to be defined. In this report, the specific role of caspase-3 in radiotherapy-induced apoptosis was studied using MCF-7 control (MCF-7/pv, caspase-3 deficient) and caspase-3 reconstituted MCF-7 (MCF-7/c3) breast cancer cells. Caspase-3 reconstitution significantly enhanced radiation-induced apoptosis, with a decrease in the survival fraction, an increase in caspase activation, cleavage of cellular death substrates and mitochondrial depolarization. We also found that the activation of caspase-7 was caspase-3-dependent in radiation-induced apoptosis, which suggests a mini-cascade among the effector caspases and that caspase-3 is essential for signal amplification. In comparing the patterns of death substrates cleavage in radiation-induced apoptosis with that in doxorubicin and TNF-α-induced apoptosis, we found that cleavage of lamin B and β-actin was relatively more susceptible to radiation, which is enhanced in the presence of caspase-3, suggesting cytoskeleton proteins might be preferred markers for radiation-induced apoptosis. These data indicate that caspase-3 plays a critical role in radiotherapy-induced apoptosis, and suggest that caspase-3 deficiency may contribute to the radioresistance of breast cancers.

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June 2005
Volume 26 Issue 6

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

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Spandidos Publications style
Yang XH, Edgerton S and Thor AD: Reconstitution of caspase-3 sensitizes MCF-7 breast cancer cells to radiation therapy. Int J Oncol 26: 1675-1680, 2005
APA
Yang, X.H., Edgerton, S., & Thor, A.D. (2005). Reconstitution of caspase-3 sensitizes MCF-7 breast cancer cells to radiation therapy. International Journal of Oncology, 26, 1675-1680. https://doi.org/10.3892/ijo.26.6.1675
MLA
Yang, X. H., Edgerton, S., Thor, A. D."Reconstitution of caspase-3 sensitizes MCF-7 breast cancer cells to radiation therapy". International Journal of Oncology 26.6 (2005): 1675-1680.
Chicago
Yang, X. H., Edgerton, S., Thor, A. D."Reconstitution of caspase-3 sensitizes MCF-7 breast cancer cells to radiation therapy". International Journal of Oncology 26, no. 6 (2005): 1675-1680. https://doi.org/10.3892/ijo.26.6.1675