Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death

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Antiestrogens are currently used for treating breast cancer patients who have estrogen receptor-positive tumors. However, patients with advanced disease will eventually develop resistance to the drugs. Therefore, compounds effective on antiestrogen-resistant tumors will be of great importance for future breast cancer treatment. In this study, we have investigated the effect of the chemotherapeutic compound cisplatin using a panel of antiestrogen-resistant breast cancer cell lines established from the human breast cancer cell line MCF-7. We show that the antiestrogen-resistant cells are significantly more sensitive to cisplatin-induced cell death than antiestrogen-sensitive MCF-7 cells and we show that cisplatin induces cell death by activating both the caspase and lysosomal death pathways. The antiestrogen-resistant cell lines express lower levels of antiapoptotic Bcl-2 protein compared with parental MCF-7 cells. Our data show that Bcl-2 can protect antiestrogen-resistant breast cancer cells from cisplatin-induced cell death, indicating that the reduced expression of Bcl-2 in the antiestrogen-resistant cells plays a role in sensitizing the cells to cisplatin treatment.
Original languageEnglish
JournalMolecular Cancer Therapeutics
Issue number6
Pages (from-to)1869-1876
Number of pages8
Publication statusPublished - Jun 2007

    Research areas

  • Antineoplastic Agents, Blotting, Western, Breast Neoplasms, Caspases, Cell Death, Cell Line, Tumor, Cisplatin, Estrogen Receptor Modulators, Humans, Peptide Hydrolases

ID: 4043846