NF-κB suppression provokes the sensitization of hormone-resistant breast cancer cells to estrogen apoptosis

The progression of breast cancer cells to estrogen-independent growth may be accompanied with the paradoxical cell sensitization to estrogen apoptotic action; however, the mechanism of this phenomenon is still unclear. In the present study, we have shown that the sensitization of hormone-resistant breast cancer cells to estrogen apoptotic action is accompanied with the gradual NF-kappa B suppression. Using the chemical inhibitors of NF-kappa B as well as the dominant-negative NF-kappa B constructs, we have proved the sufficiency of NF-kappa B inhibition for the sensitization of the resistant cells to estrogen apoptosis. Estradiol treatment results in the additional suppression of NF-kappa B, demonstrating the possible NF-kappa B involvement in the regulation of cell response to estrogens. Totally, the results presented suggest that the constitutive NF-kappa B suppression in the estrogen-independent cells may be considered as one of the factors resulting in a imbalance between pro- and anti-apoptotic pathways and enhancement in estrogen apoptotic action in the cells.