Oxidative stress and hepatocarcinogenesis

Fu, Ying; Chung, Fung‐Lung

doi:10.20517/2394-5079.2018.29

Cited by 68 publications

(51 citation statements)

References 84 publications

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“…The same study revealed that the Keap1–Nrf2 (Kelch-like ECH-associated protein 1- Nrf2) system plays a central role in the protection of cells against oxidative and xenobiotic stresses [ 91 ]. Importantly, oxidative stress has emerged as a crucial player in HCC development and progression as 90% of HCC arise in the context of chronic liver inflammation, which leads to oxidative stress, generating excess reactive oxygen species (ROS) [ 92 , 93 ]. Nrf2-Keap1 system appeared also as an important metabolic regulator that redirects glucose and glutamine into the anabolic PPP in cancer cells [ 90 ].…”

Section: Rat Models Of Hccmentioning

confidence: 99%

Animal Models: A Useful Tool to Unveil Metabolic Changes in Hepatocellular Carcinoma

Serra

Columbano

Perra

et al. 2020

Cancers

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Hepatocellular carcinoma (HCC) is one the most frequent and lethal human cancers. At present, no effective treatment for advanced HCC exist; therefore, the overall prognosis for HCC patients remains dismal. In recent years, a better knowledge of the signaling pathways involved in the regulation of HCC development and progression, has led to the identification of novel potential targets for therapeutic strategies. However, the obtained benefits from current therapeutic options are disappointing. Altered cancer metabolism has become a topic of renewed interest in the last decades, and it has been included among the core hallmarks of cancer. In the light of growing evidence for metabolic reprogramming in cancer, a wide number of experimental animal models have been exploited to study metabolic changes characterizing HCC development and progression and to further expand our knowledge of this tumor. In the present review, we discuss several rodent models of hepatocarcinogenesis, that contributed to elucidate the metabolic profile of HCC and the implications of these changes in modulating the aggressiveness of neoplastic cells. We also highlight the apparently contrasting results stemming from different animal models. Finally, we analyze whether these observations could be exploited to improve current therapeutic strategies for HCC.

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Section: Rat Models Of Hccmentioning

confidence: 99%

Animal Models: A Useful Tool to Unveil Metabolic Changes in Hepatocellular Carcinoma

Serra

Columbano

Perra

et al. 2020

Cancers

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“…The latter findings are in line with previous reports in human samples and murine models. 53 We further performed a PCA analysis and confirmed that in liver and heart, α-dC composed a joint group with AST/ALT as a marker of liver injury and significantly correlated with each other in the NAFLD model. Importantly, we also confirmed higher levels of α-dC in the NRAS G12V /p19 Arf-/-HCC model.…”

Section: Discussionmentioning

confidence: 53%

Increase of α-dicarbonyls in liver and receptor for advanced glycation end products on immune cells are linked to nonalcoholic fatty liver disease and liver cancer

et al. 2021

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Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with a very poor prognosis and constantly growing incidence. Among other primary risks of HCC, metabolic disorders and obesity have been extensively investigated over recent decades. The latter can promote nonalcoholic fatty liver disease (NAFLD) leading to the inflammatory form of nonalcoholic steatohepatitis (NASH), that, in turn, promotes HCC. Molecular determinants of this pathogenic progression, however, remain largely undefined. In this study, we have focussed on the investigation of α-dicarbonyl compounds (α-dC), highly reactive and tightly associated with overweight-induced metabolic disorders, and studied their potential role in NAFLD and progression toward HCC using murine models. NAFLD was induced using high-fat diet (HFD). Autochthonous HCC was induced using transposon-based stable intrahepatic overexpression of oncogenic NRAS G12V in mice lacking p19 Arf tumor suppressor. Our study demonstrates that the HFD regimen and HCC resulted in strong upregulation of α-dC in the liver, heart, and muscles. In addition, an increase in α-dC was confirmed in sera of NAFLD and NASH patients. Furthermore, higher expression of the receptor for advanced glycation products (RAGE) was detected exclusively on immune cells and not on stroma cells in livers of mice with liver cancer progression. Our work confirms astable interplay of liver inflammation, carbonyl stress mediated by α-dC, and upregulated RAGE expression on CD8 + Tand natural killer (NK) cells in situ in NAFLD and HCC, as key factors/determinants in liver disease progression. The obtained findings underline the role of α-dC and RAGE + CD8 + Tand RAGE + NK cells as biomarkers and candidates for a local therapeutic intervention in NAFLD and malignant liver disease.

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“…When these mitochondrial abnormalities are accompanied by diminished intracellular antioxidant protection in NASH, pathways of fatty acid metabolism are altered [63] , which, in turn, can cause metabolic stress [63] . Overproduction of ROS frequently occurs in cancer, and is believed to play an important role in the development of HCC [64] . Intriguingly, oxidative stress and abnormal methylation of tumour suppressor genes are found the livers of NAFLD patients [65] .…”

Section: Metabolic Pathwaysmentioning

confidence: 99%

Molecular links between non-alcoholic fatty liver disease and hepatocellular carcinoma

Raza¹,

Rajak²,

Anjum³

et al. 2019

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Non-alcoholic fatty liver disease (NAFLD) and its advanced complication, non-alcoholic steatohepatitis (NASH), have become leading causes of hepatocellular carcinoma (HCC) worldwide. In this review, we discuss the role of metabolic, gut microbial, immune and endocrine mediators which promote the progression of NAFLD to HCC. In particular, this progression involves multiple hits resulting from lipotoxicity, oxidative stress, inhibition of hepatic autophagy and inflammation. Furthermore, dysbiosis in the gut associated with obesity also promotes HCC via induction of proinflammatory cytokines and Toll like receptor signalling as well as altered bile metabolism. Additionally, compromised T-cell function and impaired hepatic hormonal action promote the development of NASH-associated HCC. Lastly, we discuss the current challenges involved in the diagnosis and treatment of NAFLD/NASH-associated HCC.

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Oxidative stress and hepatocarcinogenesis

Cited by 68 publications

References 84 publications

Animal Models: A Useful Tool to Unveil Metabolic Changes in Hepatocellular Carcinoma

Animal Models: A Useful Tool to Unveil Metabolic Changes in Hepatocellular Carcinoma

Increase of α-dicarbonyls in liver and receptor for advanced glycation end products on immune cells are linked to nonalcoholic fatty liver disease and liver cancer

Molecular links between non-alcoholic fatty liver disease and hepatocellular carcinoma

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