Fundamentals of cancer metabolism

Science Advances, Journal Year: 2016, Volume and Issue: 2(5)

Published: May 6, 2016

Researchers provide a conceptual framework to understand current knowledge of the fundamentals cancer metabolism.

Language: Английский

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The multifaceted contributions of mitochondria to cellular metabolism

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 20(7), P. 745 - 754

Published: June 22, 2018

Language: Английский

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Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

Chemical Reviews, Journal Year: 2017, Volume and Issue: 117(15), P. 10043 - 10120

Published: June 27, 2017

Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, effective way to deliver drugs specifically mitochondria is by covalent linking a lipophilic cation such an alkyltriphenylphosphonium moiety pharmacophore interest. Other delocalized cations, rhodamine, natural synthetic mitochondria-targeting peptides, nanoparticle vehicles, have also been used mitochondrial delivery small molecules. Depending on approach used, cell membrane potentials, more than 1000-fold higher concentration can be achieved. Mitochondrial targeting has developed study physiology dysfunction interaction between other subcellular organelles treatment variety diseases neurodegeneration cancer. In this Review, we discuss efforts target small-molecule compounds probing function, diagnostic tools potential therapeutics. We describe physicochemical basis accumulation chemistry strategies mitochondria, probes, sensors, examples bioactive compounds. Finally, review published attempts apply mitochondria-targeted agents cancer neurodegenerative

Language: Английский

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Calcium and ROS: A mutual interplay

Redox Biology, Journal Year: 2015, Volume and Issue: 6, P. 260 - 271

Published: Aug. 11, 2015

Calcium is an important second messenger involved in intra- and extracellular signaling cascades plays essential role cell life death decisions. The Ca2+ network works many different ways to regulate cellular processes that function over a wide dynamic range due the action of buffers, pumps exchangers on plasma membrane as well internal stores. pathways interact with other systems such reactive oxygen species (ROS). Although initially considered be potentially detrimental byproducts aerobic metabolism, it now clear ROS generated sub-toxic levels by intracellular act molecules various including growth death. Increasing evidence suggests mutual interplay between calcium which seems have implications for fine tuning networks. However, dysfunction either might affect system thus potentiating harmful effects contribute pathogenesis disorders.

Language: Английский

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MYC, Metabolism, and Cancer

Cancer Discovery, Journal Year: 2015, Volume and Issue: 5(10), P. 1024 - 1039

Published: Sept. 18, 2015

Abstract The MYC oncogene encodes a transcription factor, MYC, whose broad effects make its precise oncogenic role enigmatically elusive. evidence to date suggests that triggers selective gene expression amplification promote cell growth and proliferation. Through targets, coordinates nutrient acquisition produce ATP key cellular building blocks increase mass trigger DNA replication division. In cancer, genetic epigenetic derangements silence checkpoints unleash MYC's growth– proliferation-promoting metabolic activities. Unbridled in response deregulated creates dependence on MYC-driven pathways, such reliance specific enzymes provides novel targets for cancer therapy. Significance: activity are tightly regulated normal cells by multiple mechanisms, including upon factor stimulation replete status. deregulation of loss checkpoint components, as TP53, permit drive malignant transformation. However, because the cancers synthetic lethal interactions between overexpression enzyme inhibitors provide therapeutic opportunities. Cancer Discov; 5(10); 1024–39. ©2015 AACR.

Language: Английский

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Self-Assembled Copper–Amino Acid Nanoparticles for in Situ Glutathione “AND” H₂O₂ Sequentially Triggered Chemodynamic Therapy

Journal of the American Chemical Society, Journal Year: 2018, Volume and Issue: 141(2), P. 849 - 857

Published: Dec. 13, 2018

Nanoformulations that can respond to the specific tumor microenvironment (TME), such as a weakly acidic pH, low oxygen, and high glutathione (GSH), show promise for killing cancer cells with minimal invasiveness specificity. In this study, we demonstrate self-assembled copper-amino acid mercaptide nanoparticles (Cu-Cys NPs) in situ glutathione-activated H2O2-reinforced chemodynamic therapy drug-resistant breast cancer. After endocytosis into cells, Cu-Cys NPs could first react local GSH, induce GSH depletion, reduce Cu2+ Cu+. Subsequently, generated Cu+ would H2O2 generate toxic hydroxyl radicals (·OH) via Fenton-like reaction, which has fast reaction rate TME, are responsible tumor-cell apoptosis. Due concentration sequentially triggers redox reactions, exhibited relatively cytotoxicity whereas normal were left alive. The vivo results also proved efficiently inhibited without causing obvious systemic toxicity. As novel copper nanoformulation responsive these may have great potential therapy.

Language: Английский

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Oxidative Phosphorylation as an Emerging Target in Cancer Therapy

Clinical Cancer Research, Journal Year: 2018, Volume and Issue: 24(11), P. 2482 - 2490

Published: Feb. 2, 2018

Abstract Cancer cells have upregulated glycolysis compared with normal cells, which has led many to the assumption that oxidative phosphorylation (OXPHOS) is downregulated in all cancers. However, recent studies shown OXPHOS can be also certain cancers, including leukemias, lymphomas, pancreatic ductal adenocarcinoma, high subtype melanoma, and endometrial carcinoma, this occur even face of active glycolysis. inhibitors could therefore used target cancer subtypes alleviate therapeutically adverse tumor hypoxia. Several drugs metformin, atovaquone, arsenic trioxide are clinically for non-oncologic indications, but emerging data demonstrate their potential use as inhibitors. We highlight novel applications a suitable therapeutic index cell metabolism. Clin Res; 24(11); 2482–90. ©2018 AACR.

Language: Английский

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Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH

Science, Journal Year: 2015, Volume and Issue: 350(6266), P. 1391 - 1396

Published: Nov. 6, 2015

Getting all stressed out by vitamin C Few experimental cancer therapies have incited as much debate C. Yet the mechanistic effect of on cells is still poorly understood. Yun et al. studied human colorectal with KRAS or BRAF mutations and found that they “handle” in a different way than other cells, ultimately to their detriment (see Perspective Reczek Chandel). Because certain receptor up-regulated mutant take up oxidized form (dehydroascorbate). This leads oxidative stress, inactivation glycolytic enzyme required for growth, finally cell death. Whether selective toxicity these can be exploited therapeutically remains unclear. Science , this issue p. 1391 ; see also 1317

Language: Английский

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Autophagy and Tumor Metabolism

Cell Metabolism, Journal Year: 2017, Volume and Issue: 25(5), P. 1037 - 1043

Published: May 1, 2017

Language: Английский

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Mitochondria as a therapeutic target for common pathologies

Nature Reviews Drug Discovery, Journal Year: 2018, Volume and Issue: 17(12), P. 865 - 886

Published: Nov. 5, 2018

Language: Английский

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