Elucidating the multimodal anticancer mechanism of an organometallic terpyridine platinum(II) N-heterocyclic carbene complex against triple-negative breast cancer In Vitro and In Vivo
Treatment of triple-negative breast cancer (TNBC) has long been a medical challenge because of the lack of effective therapeutic targets. Targeting lipid, carbohydrate, and nucleotide metabolism pathways has recently been proven as a promising option in view of three heterogeneous metabolic-pathway-...
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| Hauptverfasser: | , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
10 March 2023
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| In: |
Journal of medicinal chemistry
Year: 2023, Jahrgang: 66, Heft: 6, Pages: 3995-4008 |
| ISSN: | 1520-4804 |
| DOI: | 10.1021/acs.jmedchem.2c01925 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1021/acs.jmedchem.2c01925
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| Verfasserangaben: | Jing-Jing Zhang, Qi-Jie Xu, Claudia Schmidt, Mohamed A. Abu el Maaty, Jinglin Song, Chunqiu Yu, Jun Zhou, Kang Han, Hao Sun, Angela Casini, Ingo Ott, and Stefan Wölfl |
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| 520 | |a Treatment of triple-negative breast cancer (TNBC) has long been a medical challenge because of the lack of effective therapeutic targets. Targeting lipid, carbohydrate, and nucleotide metabolism pathways has recently been proven as a promising option in view of three heterogeneous metabolic-pathway-based TNBC subtypes. Here, we present a multimodal anticancer platinum(II) complex, named Pt(II)caffeine, with a novel mode of action involving simultaneous mitochondrial damage, inhibition of lipid, carbohydrate, and nucleotide metabolic pathways, and promotion of autophagy. All these biological processes eventually result in a strong suppression of TNBC MDA-MB-231 cell proliferation both in vitro and in vivo. The results indicate that Pt(II)caffeine, influencing cellular metabolism at multiple levels, is a metallodrug with increased potential to overcome the metabolic heterogeneity of TNBC. | ||
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| 700 | 1 | |a Schmidt, Claudia |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Song, Jinglin |e VerfasserIn |4 aut | |
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