Tetrathiomolybdate induces dimerization of the metal-binding domain of ATPase and inhibits platination of the protein

Fang, Tiantian; Chen, Wanbiao; Sheng, Yaping; Yuan, Siming; Tang, Qiaowei; Li, Gongyu; Huang, Guangming; Su, Ji‐Hu; Zhang, Xuan; Zang, Jianye; Liu, Yangzhong

doi:10.1038/s41467-018-08102-z

Cited by 41 publications

(22 citation statements)

References 25 publications

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“…By direct binding to 3′ untranslated region (3′ UTR) of the ATP7A/B mRNA, some microRNAs (miRNA, miR) regulates the cell response to cisplatin, carboplatin, and oxaliplatin such as miR-495, miR-139, and miR-133a (Song et al, 2014;Wang et al, 2016c;Xiao et al, 2018). The copper chelator ammonium tetrathiomolybdate ([(NH 4 ) 2 MoS 4 ], TM) can also restore the sensitivity to cisplatin by inducing dimerization of the metalbinding domain of ATP7B (Fang et al, 2019).…”

Section: Atp7a and Atp7bmentioning

confidence: 99%

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

et al. 2020

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Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficiently bind to platinum agents and prevent the formation of platinum-DNA adducts, but the adducts production is the determinant step for the cytotoxicity of platinum-based antitumor agents. Even if adequate adducts have formed, tumor cells still manage to survive through increased DNA repair processes or elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum resistance. This review summarizes the critical participators of platinum resistance mechanisms mentioned above and highlights the most potential therapeutic targets or predicted markers. With a deeper understanding of the underlying resistance mechanisms, new solutions would be produced to extend the clinical application of platinum-based antitumor agents largely.

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Section: Atp7a and Atp7bmentioning

confidence: 99%

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

et al. 2020

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“…This strategy would both cut an ATP7A/B-mediated Cu supply to oncogenic Cu-binding proteins and impair ATP7A/B ability to confer cisplatin resistance through relocation towards Pt sequestration/efflux sites. Notably, a recent study demonstrates that Cu chelator tetrathiomolybdate inhibits platination of ATP7B via dimerization of MBSs [133], hence, rendering the protein less capable of driving Pt efflux from tumor cells.…”

Section: Prospectivementioning

confidence: 99%

Activity and Trafficking of Copper-Transporting ATPases in Tumor Development and Defense against Platinum-Based Drugs

Petruzzelli

Polishchuk

2019

Cells

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Membrane trafficking pathways emanating from the Golgi regulate a wide range of cellular processes. One of these is the maintenance of copper (Cu) homeostasis operated by the Golgi-localized Cu-transporting ATPases ATP7A and ATP7B. At the Golgi, these proteins supply Cu to newly synthesized enzymes which use this metal as a cofactor to catalyze a number of vitally important biochemical reactions. However, in response to elevated Cu, the Golgi exports ATP7A/B to post-Golgi sites where they promote sequestration and efflux of excess Cu to limit its potential toxicity. Growing tumors actively consume Cu and employ ATP7A/B to regulate the availability of this metal for oncogenic enzymes such as LOX and LOX-like proteins, which confer higher invasiveness to malignant cells. Furthermore, ATP7A/B activity and trafficking allow tumor cells to detoxify platinum (Pt)-based drugs (like cisplatin), which are used for the chemotherapy of different solid tumors. Despite these noted activities of ATP7A/B that favor oncogenic processes, the mechanisms that regulate the expression and trafficking of Cu ATPases in malignant cells are far from being completely understood. This review summarizes current data on the role of ATP7A/B in the regulation of Cu and Pt metabolism in malignant cells and outlines questions and challenges that should be addressed to understand how ATP7A and ATP7B trafficking mechanisms might be targeted to counteract tumor development.

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“…Smaller nanoparticles have been reported to have better biofilm penetration . Recently, several targeted drug candidates were designed for antibacterial and cancer therapy to improve therapeutic efficiency . Hence, we hypothesize that the ultrasmall‐sized and positively charged pMOF dots could possess outstanding photodynamic efficacy, excellent biofilm penetration, and bacterial targeting ability compared with bulk pMOFs.…”

Section: Introductionmentioning

confidence: 95%

Porphyrin MOF Dots–Based, Function‐Adaptive Nanoplatform for Enhanced Penetration and Photodynamic Eradication of Bacterial Biofilms

Deng

Sun

Zhang

et al. 2019

Adv Funct Materials

205

117

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Recently, antimicrobial photodynamic therapy (aPDT) has been considered as an attractive treatment option for biofilms ablation. However, even very efficient photosensitizers (PSs) still need high light doses and PS concentrations to eliminate biofilms due to the limited penetration and diffusion of PSs in biofilms. Moreover, the hypoxic microenvironment and rapid depletion of oxygen during PDT severely limit their therapeutic effects. Herein, for the first time, a porphyrin-based metal organic framework (pMOF) dots-based nanoplatform with effective biofilm penetration, self-oxygen generation, and enhanced photodynamic efficiency is synthesized for bacterial biofilms eradication. The function-adaptive nanoplatform is composed of pMOF dots encapsulated by human serum albumin-coated manganese dioxide (MnO 2 ). The pH/H 2 O 2responsive decomposition of MnO 2 in biofilms triggers the release of ultrasmall and positively charged pMOF dots and simultaneously generates O 2 insitu to alleviate hypoxia for biofilms. The released pMOF dots with high reactive oxygen species yield can effectively penetrate into biofilms, strongly bind with bacterial cell surface, and ablate bacterial biofilms. Importantly, such a nanoplatform can realize great therapeutic outcomes for treatment of Staphylococcus aureus-infected subcutaneous abscesses in vivo without damage to healthy tissues, which offers a promising strategy for efficient biofilms eradication.

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Tetrathiomolybdate induces dimerization of the metal-binding domain of ATPase and inhibits platination of the protein

Cited by 41 publications

References 25 publications

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents

Activity and Trafficking of Copper-Transporting ATPases in Tumor Development and Defense against Platinum-Based Drugs

Porphyrin MOF Dots–Based, Function‐Adaptive Nanoplatform for Enhanced Penetration and Photodynamic Eradication of Bacterial Biofilms

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