scholarly journals Tryptophan and Its Metabolites in Lung Cancer: Basic Functions and Clinical Significance

2021 ◽  
Vol 11 ◽  
Author(s):  
Chenwei Li ◽  
Hui Zhao
Keyword(s):  
Lung Cancer ◽  
Immune Suppression ◽  
Essential Amino Acid ◽  
Kynurenine Pathway ◽  
Metabolic Reprogramming ◽  
Therapeutic Drugs ◽  
Tumor Environment ◽  
Basic Functions ◽  
Pleiotropic Functions ◽  
Pathogenic Process

Lung cancer is the most lethal malignancy worldwide. Recently, it has been recognized that metabolic reprogramming is a complex and multifaceted factor, contributing to the process of lung cancer. Tryptophan (Try) is an essential amino acid, and Try and its metabolites can regulate the progression of lung cancer. Here, we review the pleiotropic functions of the Try metabolic pathway, its metabolites, and key enzymes in the pathogenic process of lung cancer, including modulating the tumor environment, promoting immune suppression, and drug resistance. We summarize the recent advance in therapeutic drugs targeting the Try metabolism and kynurenine pathway and their clinical trials.

BAI1 acts as a tumor suppressor in lung cancer A549 cells by inducing metabolic reprogramming via the SCD1/HMGCR module

2020 ◽  
Author(s):  
Lei Liu ◽  
Li Chai ◽  
Jingjing Ran ◽  
Ying Yang ◽  
Li Zhang
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Colony Formation ◽  
Warburg Effect ◽  
Poor Prognosis ◽  
A549 Cells ◽  
Angiogenesis Inhibitor ◽  
Metabolic Reprogramming ◽  
The Warburg Effect

Abstract Brain-specific angiogenesis inhibitor 1 (BAI1) is an important tumor suppressor in multiple cancers. However, the mechanisms behind its anti-tumor activity, particularly the relationship between BAI1 and metabolic aberrant of a tumor, remained unveiled. This study aimed to investigate whether BAI1 could inhibit biological functions in lung cancer A549 cells and the critical regulating molecules that induce metabolic reprogramming. Immunohistochemistry staining was performed to analyze whether variations in the expression of BAI1 in tumor tissues contributes to poor prognosis of lung cancer. Overexpressed BAI1 (BAI1-OE-A549) and control (Vector-NC-A549) were generated by lentiviral transfection. Biological function assays (proliferation, apoptosis, colony formation, invasion and in vivo metastasis), as well as metabolic reprogramming (by the Warburg effect and the glycolytic rate), were performed in both groups. Our results indicated that lower levels of BAI1 contributed to poor prognosis of lung cancer patients. Furthermore, overexpressed of BAI1 dramatically inhibited proliferation, migration, invasion, colony formation and in vivo metastasis of A549 cells. The Warburg effect and the Seahorse assay revealed that BAI1-OE induced metabolism reprogramming by inhibiting the Warburg effect and glycolysis. Further exploration indicated that BAI1 induced metabolic reprogramming by upregulating stearoyl-CoA desaturase 1 (SCD1) and inhibited 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Our study revealed a novel mechanism through which BAI1 acted as tumor suppressor by inducing metabolic reprogramming via the SCD1 and HMGCR module.

scholarly journals Role of Protein Kinase CK2 in Aberrant Lipid Metabolism in Cancer

2020 ◽  
Vol 13 (10) ◽  
pp. 292
Author(s):  
Barbara Guerra ◽  
Olaf-Georg Issinger
Keyword(s):  
Lipid Metabolism ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Intracellular Signaling ◽  
Metabolic Reprogramming ◽  
Oncogenic Signaling ◽  
Combination Strategies ◽  
Tumor Environment ◽  
Kinase Ck2

Uncontrolled proliferation is a feature defining cancer and it is linked to the ability of cancer cells to effectively adapt their metabolic needs in response to a harsh tumor environment. Metabolic reprogramming is considered a hallmark of cancer and includes increased glucose uptake and processing, and increased glutamine utilization, but also the deregulation of lipid and cholesterol-associated signal transduction, as highlighted in recent years. In the first part of the review, we will (i) provide an overview of the major types of lipids found in eukaryotic cells and their importance as mediators of intracellular signaling pathways (ii) analyze the main metabolic changes occurring in cancer development and the role of oncogenic signaling in supporting aberrant lipid metabolism and (iii) discuss combination strategies as powerful new approaches to cancer treatment. The second part of the review will address the emerging role of CK2, a conserved serine/threonine protein kinase, in lipid homeostasis with an emphasis regarding its function in lipogenesis and adipogenesis. Evidence will be provided that CK2 regulates these processes at multiple levels. This suggests that its pharmacological inhibition combined with dietary restrictions and/or inhibitors of metabolic targets could represent an effective way to undermine the dependency of cancer cells on lipids to interfere with tumor progression.

scholarly journals Kynurenine Pathway in Skin Cells: Implications for UV-Induced Skin Damage

2012 ◽  
Vol 5 ◽  
pp. IJTR.S9835 ◽  
Author(s):  
Diba Sheipouri ◽  
Nady Braidy ◽  
Gilles J. Guillemin
Keyword(s):  
Amino Acid ◽  
Essential Amino Acid ◽  
Ultra Violet ◽  
Kynurenine Pathway ◽  
Uv Exposure ◽  
Skin Damage ◽  
Skin Cells ◽  
Amino Acid Tryptophan ◽  
Inflammatory Component

The kynurenine pathway (KP) is the principle route of catabolism of the essential amino acid tryptophan, leading to the production of several neuroactive and immunoregulatory metabolites. Alterations in the KP have been implicated in various neuropsychiatric and neurodegenerative diseases, immunological disorders, and many other diseased states. Although the role of the KP in the skin has been evaluated in small niche fields, limited studies are available regarding the effect of acute ultra violet exposure and the induction of the KP in human skin-derived fibroblasts and keratinocytes. Since UV exposure can illicit an inflammatory component in skin cells, it is highly likely that the KP may be induced in these cells in response to UV exposure. It is also possible that some KP metabolites may act as pro-inflammatory and anti-inflammatory mediators, since the KP is important in immunomodulation.

scholarly journals L-tryptophan and depressive illness: a valuable adjunct to therapy?

1993 ◽  
Vol 17 (4) ◽  
pp. 223-224 ◽  
Author(s):  
Donald Eccleston
Keyword(s):  
Cerebrospinal Fluid ◽  
Amino Acid ◽  
Therapeutic Efficacy ◽  
Essential Amino Acid ◽  
Kynurenine Pathway ◽  
Depressive Illness ◽  
Western Diet ◽  
Human Nutrition ◽  
Valuable Adjunct ◽  
Original Observation

L-tryptophan is an essential amino acid in human nutrition. The minimum daily requirement for adults is in the range of 175 to 250 mg daily and this is normally exceeded in the average western diet which contains 600 to 1000 mg. Excess tryptophan is normally metabolised through the kynurenine pathway and only 1–2% of tryptophan in the diet is converted to 5-HT. The concept that 5-HT had a part to play in depressive illness evolved after the original observation by Ashcroft & Sharman in 1960 that patients with severe depressive illness had lower levels of the metabolite of 5-HT in cerebrospinal fluid compared with controls. In addition, early papers on the therapeutic efficacy of tryptophan suggested that it was potentially as successful as ECT.

scholarly journals Nrf2 Mediates Metabolic Reprogramming in Non-Small Cell Lung Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Jiangang Zhao ◽  
Xu Lin ◽  
Di Meng ◽  
Liping Zeng ◽  
Runzhou Zhuang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Metabolic Reprogramming ◽  
Related Factor ◽  
Small Cell Lung ◽  
Antioxidant Genes ◽  
Nrf2 Activation ◽  
Underlying Mechanisms

Nuclear factor erythroid-2–related factor-2 (NFE2L2/Nrf2) is a transcription factor that regulates the expression of antioxidant genes. Both Kelch-like ECH-associated protein 1 (Keap1) mutations and Nrf2 mutations contribute to the activation of Nrf2 in non-small cell lung cancer (NSCLC). Nrf2 activity is associated with poor prognosis in NSCLC. Metabolic reprogramming represents a cancer hallmark. Increasing studies reveal that Nrf2 activation promotes metabolic reprogramming in cancer. In this review, we discuss the underlying mechanisms of Nrf2-mediated metabolic reprogramming and elucidate its role in NSCLC. Inhibition of Nrf2 can alter metabolic processes, thus suppress tumor growth, prevent metastasis, and increase sensitivity to chemotherapy in NSCLC. In conclusion, Nrf2 may serve as a therapeutic target for the treatment of NSCLC.

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