7 research outputs found
Role of Interferon in Cancer Metabolism
Interferons (IFNs), a pleotropic cytokine that has long been regarded as an important effector molecule, are increasingly recognized due to their role in cancer and in antitumor immune response regulation. Interferons broadly alter cellular functions in response to viral and other infections. Dysregulation of interferon has been implicated in cancer, autoimmune disorders, and pathogenesis of chronic viral infections. However, the association between interferons and cancer cell metabolism is poorly understood. Emerging evidence suggests the importance of lipid, energy, and amino acid metabolic pathway in regulating interferon response against cancer. Additionally, viruses exploit and modulate the host cell and induce the major metabolic reprogramming causing cancer. In response, interferons upregulate the transcription of large number of interferon stimulating gene (ISG) whose products play a major role in the innate and adaptive immune response against viral infection. Immense research is being done on understanding the role of IFNs in cancer metabolism. Therefore, systematic evaluation of these associations between interferons and cancer metabolism may have important implications for the development of anticancer therapeutics targeting IFN, minimizing toxicity, and limiting off-target effects
Role of Macrophages in Solid Tumor Metabolism
Cancer cells undergo several complex processes to grow and evolve. For their survival, they manipulate the entire system and acquire the ability to gain all the energy demands from the host system itself. Tumor associated macrophages (TAMs) are macrophages abundantly present in the tumor micro environment (TME) and essentially plays a critical role in coordination with the tumor cells helping them to progress and metastasize. One of the key hallmarks in tumor cells is elevated metabolic processes such as glycolysis, fatty acid oxidation, mitochondrial oxidation, and amino acid metabolism. Macrophages help cancer cells to achieve this metabolic demand through a series of signaling events including mTOR, Akt, and PI3K pathways. The M2-like phenotype of macrophages leads to the tumorous macrophage phenotype along with the tumor cells to support tumor growth through metabolic dysregulation. Focusing upon the area of macrophage-mediated tumor metabolism in solid tumors has been a new area that provides new effective targets to treat cancer. This chapter discusses the role of macrophages in tumor metabolism and cancer progression. Targeting TAMs in tumor microenvironment through metabolic axis could be a potential therapeutic option to control the solid tumor growth and propagation
Metabolic regulation in HPV associated head and neck squamous cell carcinoma
Cancer cells exhibit distinct energy metabolic pathways due to multiple oncogenic events. In normoxia condition, the anaerobic glycolysis (Warburg effect) is highly observed in head and neck squamous cell carcinoma (HNSCC). HNSCC is associated with smoking, chewing tobacco, consumption of alcohol or Human Papillomavirus (HPV) infection primarily HPV16. In recent years, the correlation of HPV with HNSCC has significantly expanded. Despite the recent advancement in therapeutic approaches, the rate of HPV infected HNSCC has significantly increased in the last few years, specifically, in lower middle-income countries. The oncoproteins of High-risk Human Papillomavirus (HR-HPV), E6 and E7, alter the metabolic phenotype in HNSCC, which is distinct from non-HPV associated HNSCC. These oncoproteins, modulate the cell cycle and metabolic signalling through interacting with tumor suppressor proteins, p53 and pRb. Since, metabolic alteration represents a major hallmark for tumorigenesis, HPV acts as a source of biomarker linked to cancer progression in HNSCC. The dependency of cancer cells to specific nutrients and alteration of various metabolic associated genes may provide a unique opportunity for pharmacological intervention in HPV infected HNSCC. In this review, we have discussed the molecular mechanism (s) and metabolic regulation in HNSCC depending on the HPV status. We have also discussed the possible potential therapeutic approaches for HPV associated HNSCC through targeting metabolic pathways
Structure Based Drug Repurposing Through Targeting Nsp9 Replicase and Spike Proteins of SARS-CoV-2
Due to unavailability of therapeutic
approach for the novel coronavirus disease (COVID-19), the drug repurposing
approach would be the fastest and efficient way of drug development against this
deadly disease. We have applied bioinformatics approach for structure-based
drug repurposing to identify the potential inhibitors through drug screening,
molecular docking and molecular dynamics against non-structural
protein 9 (Nsp9) replicase and spike proteins of the SARS-CoV-2 from the
FDA approved drugs. We have performed virtual screening of 2000
FDA approved compounds including antiviral, anti-malarial, anti-parasitic,
anti-fungal, anti-tuberculosis and active phytochemicals against Nsp9 replicase and spike proteins of
SARS-CoV-2. Molecular docking was performed using Autodock-Vina. Selected hit compounds
were identified based on their highest binding energy and favourable ADME
profile. Notably, Conivaptan, an arginine vasopressin antagonist drug exhibited
highest binding energy (-8.4 Kcal/mol) and maximum stability with the amino
acid residues present on the active site of Nsp9 replicase. Additionally,
Tegobuvir, a non-nucleoside inhibitor of hepatitis C virus exhibited maximum
stability with highest binding energy (-8.1 Kcal/mol) on the active site of spike
protein. Molecular docking scores were further validated with the molecular
dynamics using Schrodinger, which supported strong stability of ligands with
proteins at their active site through water bridges, hydrophobic interactions,
H-bond. Overall, our findings highlight the fact that Conivaptan and Tegobuvir could
be used to control the infection and propagation of SARS-CoV-2 targeting Nsp9
replicase and spike protein, respectively. Moreover, in vitro and in vivo
validation of these findings will be helpful in bringing these molecules at the
clinical settings.</p
Metabolic regulation in HPV associated head and neck squamous cell carcinoma
Cancer cells exhibit distinct energy metabolic pathways due to multiple oncogenic events. In normoxia condition, the anaerobic glycolysis (Warburg effect) is highly observed in head and neck squamous cell carcinoma (HNSCC). HNSCC is associated with smoking, chewing tobacco, consumption of alcohol or Human Papillomavirus (HPV) infection primarily HPV16. In recent years, the correlation of HPV with HNSCC has significantly expanded. Despite the recent advancement in therapeutic approaches, the rate of HPV infected HNSCC has significantly increased in the last few years, specifically, in lower middle-income countries. The oncoproteins of High-risk Human Papillomavirus (HR-HPV), E6 and E7, alter the metabolic phenotype in HNSCC, which is distinct from non-HPV associated HNSCC. These oncoproteins, modulate the cell cycle and metabolic signalling through interacting with tumor suppressor proteins, p53 and pRb. Since, metabolic alteration represents a major hallmark for tumorigenesis, HPV acts as a source of biomarker linked to cancer progression in HNSCC. The dependency of cancer cells to specific nutrients and alteration of various metabolic associated genes may provide a unique opportunity for pharmacological intervention in HPV infected HNSCC. In this review, we have discussed the molecular mechanism (s) and metabolic regulation in HNSCC depending on the HPV status. We have also discussed the possible potential therapeutic approaches for HPV associated HNSCC through targeting metabolic pathways.Peer reviewe