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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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Main Authors: Zhang, Jing-Jing (Author) , Xu, Qi-Jie (Author) , Schmidt, Claudia (Author) , Abu El Maaty, Mohamed A. (Author) , Song, Jinglin (Author) , Yu, Chunqiu (Author) , Zhou, Jun (Author) , Han, Kang (Author) , Sun, Hao (Author) , Casini, Angela (Author) , Ott, Ingo (Author) , Wölfl, Stefan (Author)
Format: Article (Journal)
Language:English
Published: 10 March 2023
In: Journal of medicinal chemistry
Year: 2023, Volume: 66, Issue: 6, Pages: 3995-4008
ISSN:1520-4804
DOI:10.1021/acs.jmedchem.2c01925
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1021/acs.jmedchem.2c01925
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Author Notes: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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Summary: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.
Item Description:Gesehen am 26.04.2023
Physical Description:Online Resource
ISSN:1520-4804
DOI:10.1021/acs.jmedchem.2c01925

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