NAD(P)H:quinone oxidoreductase 1 (NQO1) in the sensitivity and resistance to antitumor quinones.
David Siegel,Chao Yan,David Ross +2 more
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TLDR
The role of NQO1 in the sensitivity and resistance of human cancers to the quinone antitumor drugs mitomycin C, β-lapachone and the benzoquinone ansamycin class of Hsp90 inhibitors including 17-AAG is discussed.About:
This article is published in Biochemical Pharmacology.The article was published on 2012-04-15 and is currently open access. It has received 238 citations till now. The article focuses on the topics: NAD(P)H Dehydrogenase (Quinone).read more
Citations
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Co-occurring Genomic Alterations Define Major Subsets of KRAS-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities
Ferdinandos Skoulidis,Lauren Averett Byers,Lixia Diao,Vassiliki A. Papadimitrakopoulou,Pan Tong,Julie G. Izzo,Carmen Behrens,Humam Kadara,Edwin Roger Parra,Jaime Rodriguez Canales,Jianjun Zhang,Uma Giri,Jayanthi Gudikote,Maria Angelica Cortez,Chao Yang,You Hong Fan,Michael Peyton,Luc Girard,Kevin R. Coombes,Carlo Toniatti,Timothy P. Heffernan,Murim Choi,Garrett M. Frampton,Vincent A. Miller,John N. Weinstein,Roy S. Herbst,Kwok-Kin Wong,Jianhua Zhang,Padmanee Sharma,Gordon B. Mills,Waun Ki Hong,John D. Minna,James P. Allison,Andrew Futreal,Jing Wang,Ignacio I. Wistuba,John V. Heymach +36 more
TL;DR: Evidence is provided that co-occurring genomic alterations identify subgroups of KRAS-mutant lung adenocarcinoma with distinct biology and therapeutic vulnerabilities, and that KL cells showed increased vulnerability to HSP90-inhibitor therapy.
Journal ArticleDOI
SoNar, a Highly Responsive NAD+/NADH Sensor, Allows High-Throughput Metabolic Screening of Anti-tumor Agents
Yuzheng Zhao,Qingxun Hu,Feixiong Cheng,Ni Su,Aoxue Wang,Yejun Zou,Hanyang Hu,Xianjun Chen,Hai-Meng Zhou,Xinzhi Huang,Kai Yang,Qian Zhu,Xue Wang,Jing Yi,Linyong Zhu,Xuhong Qian,Lixin Chen,Yun Tang,Joseph Loscalzo,Yi Yang +19 more
TL;DR: This study developed an intensely fluorescent, rapidly responsive, pH-resistant, genetically encoded sensor of wide dynamic range, denoted SoNar, for tracking cytosolic NAD(+) and NADH redox states in living cells and in vivo, and identified KP372-1 as a potent NQO1-mediated redox cycling agent that produced extreme oxidative stress, selectively induced cancer cell apoptosis, and effectively decreased tumor growth in vivo.
Journal ArticleDOI
Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment
Evguenia M. Alexandrova,Alisha R. Yallowitz,Dun Li,S Xu,Ramona Schulz,D. A. Proia,Guillermina Lozano,Matthias Dobbelstein,Ute M. Moll +8 more
TL;DR: It is shown that long-term HSP90 inhibition significantly extends the survival of mutp53 Q/− (R248Q allele) and H/H (R172H allele) mice by 59% and 48%, respectively, but not their corresponding p53−/− littermates, and drug activity correlates with induction ofmutp53 degradation, tumour apoptosis and prevention of T-cell lymphomagenesis.
Journal ArticleDOI
Nrf2 at the heart of oxidative stress and cardiac protection.
TL;DR: Multiple lines of evidence presented here support the potential of dialing up the Nrf2 pathway for cardiac protection in the clinic, including removal of Keap1 by autophagy due to p62/SQSTM1 binding, inhibition of βTrCP or Synoviolin/Hrd1-mediated ubiquitination of NRF2, and de novo Nrf1 protein translation.
Journal ArticleDOI
Understanding cancer and the anticancer activities of naphthoquinones – a review
TL;DR: The most recent applications of naphthoquinones and their derivatives in cancer drug discovery are described and the biology relevant to the design of novel naphTHoquinone anticancer agents is discussed to contribute to understanding cancer.
References
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Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation.
TL;DR: It is demonstrated that HSP participation in multimolecular complex formation is required for src-mediated transformation and can provide a target for drug modulation.
Journal ArticleDOI
Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent.
TL;DR: In consideration of the potential for acute hepatotoxic reactions to GM, as well as to the other benzoquinoid ansamycins based upon structural analogy, additional pharmacological and therapeutic information is required to ascertain whether these compounds are viable candidates for clinical development.
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The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin.
TL;DR: The biologic effects of 17-allylamino-17-demethoxygeldanamycin (17-AG), an ansamycin derivative with lower in vivo toxicity than GA, are examined, finding that it bound specifically to HSP90 in a similar manner to GA itself.
Journal ArticleDOI
Geldanamycin, a new antibiotic.
TL;DR: A new crystalline antimicrobial compound, geldanamycin, has been discovered in the culture nitrates of Streptomyces hygroscopicus var.
Journal ArticleDOI
DT-Diaphorase Expression and Tumor Cell Sensitivity to 17-Allylamino,17-demethoxygeldanamycin, an Inhibitor of Heat Shock Protein 90
TL;DR: The results suggest that the antitumor activity and possibly the toxicologic properties of 17AAG in humans may be influenced by the expression of DT-diaphorase.
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