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Issue 2, 2018
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A study on platinum(iv) species containing an estrogen receptor modulator to reverse tamoxifen resistance of breast cancer

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Abstract

Several dual-action Tam–Pt(IV) complexes derived from tamoxifen (Tam) and platinum(II) drugs were designed and synthesized for targeting estrogen receptors (ERs) 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 plays a targeting role in ER-positive tumor cells and promotes the uptake of platinum via an estrogen receptor-mediated pathway. A study on the preliminary mechanism of the typical conjugate, complex 1, revealed that the Tam–Pt(IV) complex induced apoptosis via the mitochondrial-dependent apoptosis pathway mediated through the activation of caspase 3 and PARP proteins. These results suggested that the conjugation of estrogen receptor modulators with 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.

Graphical abstract: A study on platinum(iv) species containing an estrogen receptor modulator to reverse tamoxifen resistance of breast cancer

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Supplementary files

Article information


Submitted
17 Oct 2017
Accepted
19 Dec 2017
First published
19 Dec 2017

Metallomics, 2018,10, 346-359
Article type
Paper

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