The gold compound auranofin induces apoptosis of human multiple myeloma cells through both down-regulation of STAT3 and inhibition of NF-κB activity

Nakaya, Aya; Sagawa, M.; Muto, Akihiro; Uchida, Hideo; Ikeda, Yasuo; Kizaki, Masahiro

doi:10.1016/j.leukres.2010.05.011

Cited by 85 publications

(66 citation statements)

References 48 publications

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“…In fact, it proved cytotoxic toward several human tumor cell lines, including cisplatin-sensitive and -resistant ovarian cells [104], multiple myeloma [105] and leukemia [106] cells. Unfortunately, antitumor activity was confirmed in vivo only against murine P388 lymphoma [107,108].…”

Section: Auranofin and Its Analoguesmentioning

confidence: 99%

Metal-based glycoconjugates and their potential in targeted anticancer chemotherapy

Pettenuzzo¹,

Pigot²,

Ronconi³

2016

Metallodrugs

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Glucose is a key source of energy and an essential nutrient for cell growth. Rapidly dividing cancer cells are well-known to require more nutrients and energy than normal ones to sustain their higher proliferation rates, and glucose is no exception. Therefore, the biomolecules involved in the promotion/regulation of the glycolytic flux may be regarded as potential targets for tackling tumor progression. Among all, glucose transporters (GLUTs), devoted to the recognition and cellular internalization of glucose, are largely overexpressed in tumors, thus indicating glycolysis as the major anaerobic glucose metabolism. Accordingly, such increased demand of glucose by fast-proliferating cancer cells makes it very attractive to selectively target tumor sites. In particular, tailored glucose-like substrates can be conjugated to chemotherapeutics (including metal-containing anticancer agents) so as to attain the site-specific delivery of drugs into the affected tissues. Progress in the development of metal-based glycoconjugates are here summarized and discussed.

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Section: Auranofin and Its Analoguesmentioning

confidence: 99%

Metal-based glycoconjugates and their potential in targeted anticancer chemotherapy

Pettenuzzo¹,

Pigot²,

Ronconi³

2016

Metallodrugs

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Section: Anti-neoplastic Propertiesmentioning

confidence: 99%

“…AF has been shown to reduce IL-6 release and inhibit IL-6-dependent activation of janus kinase (JAK)-1 and -2 (Kim et al 2007;Nakaya et al 2011). Inhibiting JAK-1 and -2 prevents phosphorylation of STAT-3 in multiple myeloma cell lines and AF-induced reduction in STAT-3 activity leads to decreased NF-jB activation (Kim et al 2007;Nakaya et al 2011). The combination of inhibition of STAT-3 signalling and inhibition of cellular release of TNF-a and IL-1b may contribute to the molecular mechanisms responsible for the cytotoxicity of AF towards neoplasms (Nakaya et al 2011).…”

Section: Anti-neoplastic Propertiesmentioning

confidence: 99%

“…Inhibiting JAK-1 and -2 prevents phosphorylation of STAT-3 in multiple myeloma cell lines and AF-induced reduction in STAT-3 activity leads to decreased NF-jB activation (Kim et al 2007;Nakaya et al 2011). The combination of inhibition of STAT-3 signalling and inhibition of cellular release of TNF-a and IL-1b may contribute to the molecular mechanisms responsible for the cytotoxicity of AF towards neoplasms (Nakaya et al 2011). As NF-jB activation occurs through many different pathways; including intrinsic activation via cytokines and extrinsic activation through TLRs, targeting more than one pathway may yield more effective inhibition of the development and clonal evolution of neoplasms (Balkwill and Mantovani 2001;Greten and Karin 2004).…”

Section: Anti-neoplastic Propertiesmentioning

confidence: 99%

“…While the precise mechanism of AF's anti-inflammatory activity has not been established, a range of effects of AF on peripheral inflammatory pathways have been well documented (Kim et al 2007(Kim et al , 2010Nakaya et al 2011;Stern et al 2005;Yamashita et al 1997). AF affects the secretion of several cytokines, and there have been reports of AF modulating the secretion of interleukin (IL)-8 and IL-6 from lipopolysaccharide (LPS)-stimulated monocytes and macrophages (Kim et al 2010;Stern et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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The biological activity of auranofin: implications for novel treatment of diseases

et al. 2012

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More than 30 years ago, auranofin was developed for the treatment of rheumatoid arthritis as a substitution for the injectable gold compounds aurothiomalate and aurothioglucose. Both the ease of oral administration over intramuscular injections and more potent anti-inflammatory effects in vitro made auranofin seem like an excellent substitute for the traditional injectable gold compounds. Despite efficacy in the treatment of both rheumatoid arthritis and psoriasis, currently, auranofin is seldom used as a treatment for patients with rheumatoid arthritis as more novel anti-rheumatic medications have become available. Despite the decline in its clinical applications, research on auranofin has continued as it shows promise in the treatment of several different diseases. In recent years, advances in technology have allowed researchers to use molecular techniques to identify novel mechanisms of action of auranofin. Additionally, researchers are discovering potential new applications of auranofin. Dual inhibition of inflammatory pathways and thiol redox enzymes by auranofin makes it a new candidate for cancer therapy and treating microbial infections. This review will summarize recently obtained data on the mechanisms of action of auranofin, and potential new applications of auranofin in the treatment of various diseases, including several types of leukaemia, carcinomas, and parasitic, bacterial, and viral infections.

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An Artemisinin‐Derivative–(NHC)Gold(I) Hybrid with Enhanced Cytotoxicity through Inhibition of NRF2 Transcriptional Activity

et al. 2020

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A family of hybrid complexes combining two biologically active motifs, an artemisinin derivative and a cationic bis(NHC)‐gold(I) unit, has been synthesized. One of these complexes, 2 a, has been analyzed by single‐crystal X‐ray diffraction. 2 a shows strong anticancer activities on a large panel of human cancer cell models (prostate, breast, lung, liver, bladder, bone, acute and chronic myeloid leukemias) with GI50 values in the nm range, together with a high selectivity. An original and distinctive mechanism of action, that is, through inhibition of the redox antioxidant NRF2 transcription factor (strongly associated with aggressiveness and resistance to cancer therapies) has been evidenced. 2 a could remarkably sensitize to sorafenib in HepG2 liver cells, in which dysregulated NRF2 signaling is linked to primary and acquired drug resistance. 2 a also inhibited NF‐κB and HIF transcriptional activities, which are also associated with progression and resistance in cancer. Our findings provide evidence that hybrid (NHC)gold(I) compounds represent a new class of organometallic hybrid molecules that may yield new therapeutic agents.

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The gold compound auranofin induces apoptosis of human multiple myeloma cells through both down-regulation of STAT3 and inhibition of NF-κB activity

Cited by 85 publications

References 48 publications

Metal-based glycoconjugates and their potential in targeted anticancer chemotherapy

Metal-based glycoconjugates and their potential in targeted anticancer chemotherapy

The biological activity of auranofin: implications for novel treatment of diseases

An Artemisinin‐Derivative–(NHC)Gold(I) Hybrid with Enhanced Cytotoxicity through Inhibition of NRF2 Transcriptional Activity

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