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Dysregulation of Nrf2 in Hepatocellular Carcinoma: Role in Cancer Progression and Chemoresistance

Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore 641 046, Tamilnadu, India
Stem Cell and Cancer Biology Laboratory, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6009, Australia
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2018, 10(12), 481;
Received: 31 October 2018 / Revised: 29 November 2018 / Accepted: 29 November 2018 / Published: 3 December 2018
PDF [3856 KB, uploaded 3 December 2018]


The liver executes versatile functions and is the chief organ for metabolism of toxicants/xenobiotics. Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the third foremost cause of cancer death worldwide. Oxidative stress is a key factor related with the development and progression of HCC. Nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2) is a cytosolic transcription factor, which regulates redox homeostasis by activating the expression of an array of antioxidant response element-dependent genes. Nrf2 displays conflicting roles in normal, healthy liver and HCC; in the former, Nrf2 offers beneficial effects, whereas in the latter it causes detrimental effects favouring the proliferation and survival of HCC. Sustained Nrf2 activation has been observed in HCC and facilitates its progression and aggressiveness. This review summarizes the role and mechanism(s) of action of Nrf2 dysregulation in HCC and therapeutic options that can be employed to modulate this transcription factor. View Full-Text
Keywords: hepatocellular carcinoma; Keap1-Nrf2-ARE pathway; microRNAs; Nrf2 dysregulation; phytochemicals hepatocellular carcinoma; Keap1-Nrf2-ARE pathway; microRNAs; Nrf2 dysregulation; phytochemicals

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Raghunath, A.; Sundarraj, K.; Arfuso, F.; Sethi, G.; Perumal, E. Dysregulation of Nrf2 in Hepatocellular Carcinoma: Role in Cancer Progression and Chemoresistance. Cancers 2018, 10, 481.

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