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Study on Platinum(IV) Species Containing an Estrogen Receptor Modulator to Reverse Tamoxifen Resistance of Breast Cancer

Abstract

Several dual-action Tam-Pt(IV) complexes derived from tamoxifen (Tam) and platinum(II) drugs were designed and synthesized for targeting estrogen receptor (ER) and DNA. These novel compounds not only exhibited potent cytotoxicity against breast cancer cells, but also reversed the tamoxifen resistance of TamR-MCF-7 cancer cells. Computational docking assays together with cellular uptake data demonstrated that the ER ligand portion of these conjugates play a targeting role in ER positive tumor cells and promote the uptake of platinum via estrogen receptor-mediate pathway. Preliminary mechanism study on the typical conjugate, complex 1, revealed that the Tam-Pt(IV) complex induced apoptosis by the mitochondrial-dependent apoptosis pathway mediated through the activation of caspase 3 and PARP proteins. These results suggested that conjugation of estrogen modulators to the platinum moiety could facilitate a selective enrichment of platinum in estrogen positive tumors and possibly broaden the scope of ER ligand clinical use to resistant breast tumors.

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Publication details

The article was received on 17 Oct 2017, accepted on 19 Dec 2017 and first published on 19 Dec 2017


Article type: Paper
DOI: 10.1039/C7MT00289K
Citation: Metallomics, 2017, Accepted Manuscript
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    Study on Platinum(IV) Species Containing an Estrogen Receptor Modulator to Reverse Tamoxifen Resistance of Breast Cancer

    W. Hu, J. Zhao, W. Hua and S. Gou, Metallomics, 2017, Accepted Manuscript , DOI: 10.1039/C7MT00289K

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