Gene expression profiles induced by cancer chemopreventive isothiocyanate sulforaphane in the liver of C57BL/6J mice and C57BL/6J/Nrf2 (−/−) mice

Hu, Rong; Xu, Changjiang; Shen, Guoxiang; Jain, Mohit Raja; Khor, Tin Oo; Gopalkrishnan, Avantika; Lin, Wen; Reddy, Bandaru S.; Chan, Julia Y.; Kong, Ah‐Ng Tony

doi:10.1016/j.canlet.2005.11.050

Cited by 229 publications

(167 citation statements)

References 68 publications

Supporting

Mentioning

152

Contrasting

Order By: Relevance

“…Prdx6 overexpression in keratinocytes can reduce the initiation of skin tumors, but once they arise, cancer progression is accelerated by Prdx6 overexpression (Rolfs et al 2013). Similarly, NRF2 confers resistance to chemical carcinogens but also promotes cancer progression by protecting cancer cells from oxidative stress and DNA damage (Ramos-Gomez et al 2001;Iida et al 2004;Hayes and McMahon 2006;Hu et al 2006;Xu et al 2006;Ma 2013;Satoh et al 2013). Increased NRF2 expression in human cancers correlates with a poor prognosis (Moon and Giaccia 2015).…”

Section: Ros In Cancer Initiation and Progressionmentioning

confidence: 99%

Cancer, Oxidative Stress, and Metastasis

Gill

Piskounova

Morrison

2016

Cold Spring Harb Symp Quant Biol

231

164

View full text Add to dashboard Cite

Reactive oxygen species (ROS) are highly reactive molecules that arise from a number of cellular sources, including oxidative metabolism in mitochondria. At low levels they can be advantageous to cells, activating signaling pathways that promote proliferation or survival. At higher levels, ROS can damage or kill cells by oxidizing proteins, lipids, and nucleic acids. It was hypothesized that antioxidants might benefit high-risk patients by reducing the rate of ROS-induced mutations and delaying cancer initiation. However, dietary supplementation with antioxidants has generally proven ineffective or detrimental in clinical trials. High ROS levels limit cancer cell survival during certain windows of cancer initiation and progression. During these periods, dietary supplementation with antioxidants may promote cancer cell survival and cancer progression. This raises the possibility that rather than treating cancer patients with antioxidants, they should be treated with pro-oxidants that exacerbate oxidative stress or block metabolic adaptations that confer oxidative stress resistance.

show abstract

Section: Ros In Cancer Initiation and Progressionmentioning

confidence: 99%

Cancer, Oxidative Stress, and Metastasis

Gill

Piskounova

Morrison

2016

Cold Spring Harb Symp Quant Biol

231

164

View full text Add to dashboard Cite

show abstract

“…Less is known about the regulation of ALR expression under conditions of oxidative stress. Microarray analyses using chemopreventive compounds indicate that Nrf2 regulates expression of cytoprotective proteins including ALR (gene: Gfer) leading to secondary protection against DNA or protein damage which enhances cell survival (28,29).…”

Section: Introductionmentioning

confidence: 99%

Nrf2 Activates Augmenter of Liver Regeneration (ALR) via Antioxidant Response Element and Links Oxidative Stress to Liver Regeneration

Dayoub

Vogel

Schuett

et al. 2013

Mol Med

View full text Add to dashboard Cite

Liver regeneration can be impaired by permanent oxidative stress and activation of nuclear factor erythroid 2-related factor 2 (Nrf2), known to regulate the cellular antioxidant response, and has been shown to improve the process of liver regeneration. A variety of factors regulate hepatic tissue regeneration, among them augmenter of liver regeneration (ALR), attained great attention as being survival factors for the liver with proproliferative and antiapoptotic properties. Here we determined the Nrf2/ antioxidant response element (ARE) regulated expression of ALR and show ALR as a target gene of Nrf2 in vitro and in vivo. The ALR promoter comprises an ARE binding site and, therefore, ALR expression can be induced by ARE-activator tertiary butylhydroquinone (tBHQ) in hepatoma cells and primary human hepatocytes (PHH). Promoter activity and expression of ALR were enhanced after cotransfection of Nrf2 compared with control and dominant negative mutant of Nrf2. Performing partial hepatectomy in livers from Nrf2+/+ mice compared with Nrf2−/− knock-out (KO) mice, we found increased expression of ALR in addition to known antioxidant ARE-regulated genes. Furthermore, we observed increased ALR expression in hepatitis B virus (HBV) compared with hepatitis C virus (HCV) positive hepatoma cells and PHH. Recently, it was demonstrated that HBV infection activates Nrf2 and, now, we add results showing increased ALR expression in liver samples from patients infected with HBV. ALR is regulated by Nrf2, acts as a liver regeneration and antioxidative protein and, therefore, links oxidative stress to hepatic regeneration to ensure survival of damaged cells.

show abstract

“…However, the mammalian homolog of Rpn4 has not been identified so far. Instead, other transcription factors seem to be involved, in particular, the antioxidative transcription factor, nuclear factor E2-related factor 2 (Nrf2) (Kwak et al, 2003;Hu et al, 2006;Kwak and Kensler, 2006;Arlt et al, 2007), which is also a target protein of 26S-Pr. Nrf2 is mainly involved in cellular phase II responses to oxidative stress and is under the control of the Keap1 regulatory protein in a redox-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

“…In response to oxidative stress (reactive oxygen species (ROS) and glutathione (GSH) depletion) and electrophilic insults (that is, by antioxidants such as tert-butylhydroquinone (tBHQ) or sulforaphane) (Ishii et al, 2000;Huang et al, 2002;Wakabayashi et al, 2004;Cho et al, 2005), the E3-ligase adaptor, Keap1, dissociates from Nrf2, thereby releasing it from polyubiquitination and proteasomal degradation (Itoh et al, 1999). Nrf2 then enters the nucleus and induces antioxidant target genes and also a number of proteasomal proteins (Hu et al, 2006). Along with others, we have shown that many of the proteasomal subunit genes possess an antioxidant response element in their promoter, which is under the control of Nrf2 (Kwak et al, 2003;Kwak and Kensler, 2006;Arlt et al, 2007).…”

Section: Introductionmentioning

confidence: 99%