Glutathione metabolism in cancer progression and treatment resistance

The Journal of Cell Biology, Journal Year: 2018, Volume and Issue: 217(7), P. 2291 - 2298

Published: June 18, 2018

Glutathione (GSH) is the most abundant antioxidant found in living organisms and has multiple functions, of which maintain cellular redox homeostasis. GSH preserves sufficient levels cysteine detoxifies xenobiotics while also conferring therapeutic resistance to cancer cells. However, metabolism plays both beneficial pathogenic roles a variety malignancies. It crucial removal detoxification carcinogens, alterations this pathway can have profound effect on cell survival. Excess promotes tumor progression, where elevated correlate with increased metastasis. In review, we discuss recent studies that focus deciphering role initiation progression as well mechanisms underlying how imparts treatment growing cancers. Targeting synthesis/utilization therefore represents potential means rendering cells more susceptible different options such chemotherapy radiotherapy.

Language: Английский

---

Endoplasmic reticulum stress signals in the tumour and its microenvironment

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 21(2), P. 71 - 88

Published: Nov. 19, 2020

Language: Английский

---

Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion

Science, Journal Year: 2019, Volume and Issue: 366(6468), P. 1013 - 1021

Published: Nov. 8, 2019

The metabolic characteristics of tumors present considerable hurdles to immune cell function and cancer immunotherapy. Using a glutamine antagonist, we metabolically dismantled the immunosuppressive microenvironment tumors. We demonstrate that blockade in tumor-bearing mice suppresses oxidative glycolytic metabolism cells, leading decreased hypoxia, acidosis, nutrient depletion. By contrast, effector T cells responded antagonism by markedly up-regulating adopting long-lived, highly activated phenotype. These divergent changes cellular programming form basis for potent antitumor responses. Glutamine therefore exposes previously undefined difference plasticity between can be exploited as "metabolic checkpoint" tumor

Language: Английский

---

Application of glutathione depletion in cancer therapy: Enhanced ROS-based therapy, ferroptosis, and chemotherapy

Biomaterials, Journal Year: 2021, Volume and Issue: 277, P. 121110 - 121110

Published: Aug. 30, 2021

Language: Английский

---

Glutamine reliance in cell metabolism

Experimental & Molecular Medicine, Journal Year: 2020, Volume and Issue: 52(9), P. 1496 - 1516

Published: Sept. 1, 2020

Abstract As knowledge of cell metabolism has advanced, glutamine been considered an important amino acid that supplies carbon and nitrogen to fuel biosynthesis. A recent study provided a new perspective on mitochondrial metabolism, offering mechanistic insights into metabolic adaptation during tumor hypoxia, the emergence drug resistance, glutaminolysis-induced reprogramming presenting strategies target in cancer cells. In this review, we introduce various biosynthetic bioenergetic roles based compartmentalization explain why cells exhibit reliance glutamine. Additionally, examined whether derivatives contribute epigenetic regulation associated with tumorigenesis. addition, discussing transporters, propose for therapeutic intervention cancer.

Language: Английский

---

Mechanisms and Implications of Metabolic Heterogeneity in Cancer

Cell Metabolism, Journal Year: 2019, Volume and Issue: 30(3), P. 434 - 446

Published: Sept. 1, 2019

Language: Английский

---

N6-methyladenosine links RNA metabolism to cancer progression

Cell Death and Disease, Journal Year: 2018, Volume and Issue: 9(2)

Published: Jan. 26, 2018

Abstract N6-methyladenosine (m6A) is the most abundant mRNA modification. With development of antibody-based sequencing technologies and findings m6A-related “writers”, “erasers”, “readers”, relationships between m6A metabolism are emerging. The modification influences almost every step RNA that comprises processing, exporting from nucleus to cytoplasm, translation, decay, biogenesis long-non-coding (lncRNA) microRNA (miRNA). Recently, more studies have found associated with cancer, contributing self-renewal cancer stem cell, promotion cell proliferation, resistance radiotherapy or chemotherapy. Inhibitors factors been explored, some them were identified inhibit progression, indicating could be a target for therapy. In this review, we trying summarize regulation function in human carcinogenesis.

Language: Английский

---

Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation

Cells, Journal Year: 2021, Volume and Issue: 10(5), P. 1056 - 1056

Published: April 29, 2021

Cancer cells alter metabolic processes to sustain their characteristic uncontrolled growth and proliferation. These alterations include (1) a shift from oxidative phosphorylation aerobic glycolysis support the increased need for ATP, (2) glutaminolysis NADPH regeneration, (3) altered flux through pentose phosphate pathway tricarboxylic acid cycle macromolecule generation, (4) lipid uptake, lipogenesis, cholesterol synthesis, (5) upregulation of one-carbon metabolism production NADH/NADPH, nucleotides, glutathione, (6) amino metabolism, (7) metabolism-based regulation apoptosis, (8) utilization alternative substrates, such as lactate acetate. Altered in cancer is controlled by tumor-host cell interactions, key oncogenes, tumor suppressors, other regulatory molecules, including non-coding RNAs. Changes pathways are dynamic, exhibit plasticity, often dependent on type microenvironment, leading thought Warburg Effect "reverse Effect" plasticity. Understanding complex nature these multiple can development new therapies.

Language: Английский

---

Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 12(2), P. 558 - 580

Published: Sept. 27, 2021

Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies treat HCC, such as targeted tyrosine kinase inhibitors, immune based and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation progression driven by reprogramming metabolism, particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal new nomenclature non-alcoholic (NAFLD), indicates growing appreciation metabolism the pathogenesis disease, thereby suggesting targeting abnormal treatment. In this review, we introduce directions highlighting targets glucose, acid, amino acid glutamine which are suitable intervention. We also summarize discuss agents studies deregulated Furthermore, opportunities challenges discovery development therapy discussed.

Language: Английский

---

Cancer-associated adipocytes: key players in breast cancer progression

Journal of Hematology & Oncology, Journal Year: 2019, Volume and Issue: 12(1)

Published: Sept. 9, 2019

Adipocytes are one of the primary stromal cells in many tissues, and they considered to play an active role tumor microenvironment. Cancer-associated adipocytes (CAAs) not only found adjacent cancer cells, but also communicate with through releasing various factors that can mediate local systemic effects. The adipocyte-cancer cell crosstalk leads phenotypical functional changes both types, which further enhance progression. Indeed, obesity, is associated increase adipose mass alteration tissue, becoming pandemic some countries it now be independent risk factor for In this review, we focus on potential mechanisms involved special attention circle breast cancer. We envisage besides having a direct impact CAAs systemically preconditions microenvironment by favoring anti-tumor immunity. A better understanding cancer-associated key molecular events will provide insights into biology permit optimization therapeutic strategies.

Language: Английский

---