Downregulation of Nrf2 by the combination of TRAIL and Valproic acid induces apoptotic cell death of TRAIL-resistant papillary thyroid cancer cells via suppression of Bcl-xL

Cha, Hyun-Young; Lee, Bok‐Soon; Chang, Jae Won; Park, Ju Kyeong; Han, Jae Ho; Kim, Yong‐Sung; Shin, Yoo Seob; Byeon, Hyung Kwon; Kim, Chul‐Ho

doi:10.1016/j.canlet.2015.12.016

Cited by 30 publications

(20 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ziros et al demonstrated Nrf2 hyperactivity in PTC by immunohistochemical detection of Nrf2 and its target, Nqo1, in tumor cells compared with normal thyroid tissues. On the other hand, an in vitro study demonstrated downregulation of Nrf2 inducing apoptotic cell death in PTC treated with tumor necrosis factor‐related associated‐inducing ligand (TRAIL) and valproic acid …”

Section: Discussionmentioning

confidence: 99%

Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2‐Keap1 interaction: Activation of antioxidative pathway in papillary thyroid carcinoma

et al. 2018

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2‐Keap1 interaction: Activation of antioxidative pathway in papillary thyroid carcinoma

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Nuclear factor E2-related factor 2 (NRF2) is a leucine zipper transcription factor and plays an important role in the maintenance of redox homeostasis. When subjected to oxidative stress, NRF2 is stabilized, accumulated, and translocates to the nucleus, where it binds to a specific DNA sequence, referred to as the antioxidant response element (ARE), and induces the expression of a cohort of cytoprotective enzyme genes (19,20). NRF2 and the ARE-driven genes it controls are frequently upregulated in PDAC and correlate with poor survival.…”

Section: Introductionmentioning

confidence: 99%

PIN1 Maintains Redox Balance via the c-Myc/NRF2 Axis to Counteract Kras-Induced Mitochondrial Respiratory Injury in Pancreatic Cancer Cells

Liang

Shi

et al. 2019

Cancer Research

View full text Add to dashboard Cite

Kras is a decisive oncogene in pancreatic ductal adenocarcinoma (PDAC). PIN1 is a key effector involved in the Kras/ERK axis, synergistically mediating various cellular events. However, the underlying mechanism by which PIN1 promotes the development of PDAC remains unclear. Here we sought to elucidate the effect of PIN1 on redox homeostasis in Kras-driven PDAC. PIN1 was prevalently upregulated in PDAC and predicted the prognosis of the disease, especially Kras-mutant PDAC. Downregulation of PIN1 inhibited PDAC cell growth and promoted apoptosis, partially due to mitochondrial dysfunction. Silencing of PIN1 damaged basal mitochondrial function by significantly increasing intracellular ROS. Furthermore, PIN1 maintained redox balance via synergistic activation of c-Myc and NRF2 to upregulate expression of antioxidant response element driven genes in PDAC cells. This study elucidates a new mechanism by which Kras/ERK/NRF2 promotes tumor growth and identifies PIN1 as a decisive target in therapeutic strategies aimed at disturbing the redox balance in pancreatic cancer.Significance: This study suggests that antioxidation protects Kras-mutant pancreatic cancer cells from oxidative injury, which may contribute to development of a targeted therapeutic strategy for Kras-driven PDAC by impairing redox homeostasis.

show abstract

“…Under inflammatory and oxidative stress conditions, elevated ROS can enhance Keap1 oxidation causing release of Nrf2. After translocation to the nucleus, Nrf2 binds to the antioxidant response element (ARE) initiating expression of antioxidative genes such as heme oxygenase-1 (HO-1), superoxide dismutases (SODs), NAD(P)H:quinone oxidoreductase 1 (NQO1), uridine 5′diphospho-glucuronosyl transferase enzymes (UGTs), glutathione cysteine ligase (GCL) and glutathione reductase (GR) to scavenge excessive ROS (Cha et al, 2016 ; Xue et al, 2016 ; Wasik et al, 2017 ). SODs catalyze the dismutation of O 2 − to form O 2 and H 2 O 2 , which can then be converted to H 2 O. GCL and GR regulate the generation and metabolism of glutathione (GSH), which is a crucial antioxidant to maintain cellular redox status (Zhang et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Valproic Acid Attenuates Traumatic Brain Injury-Induced Inflammation in Vivo: Involvement of Autophagy and the Nrf2/ARE Signaling Pathway

Chen

Wang

Zhou

et al. 2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Microglial activation and the inflammatory response in the central nervous system (CNS) play important roles in secondary damage after traumatic brain injury (TBI). Transcriptional activation of genes that limit secondary damage to the CNS are mediated by a cis-acting element called the antioxidant responsive element (ARE). ARE is known to associate with the transcription factor NF-E2-related factor 2 (Nrf2), a transcription factor that is associated with histone deacetylases (HDACs). This pathway, known as the Nrf2/ARE pathway, is a critical antioxidative factor pathway that regulates the balance of oxygen free radicals and the inflammatory response, and is also related to autophagic activities. Although valproic acid (VPA) is known to inhibit HDACs, it is unclear whether VPA plays a role in the microglia-mediated neuroinflammatory response after TBI via regulating oxidative stress and autophagy induced by the Nrf2/ARE signaling pathway. In this study, we demonstrate that microglial activation, oxidative stress, autophagy, and the Nrf2/ARE signaling pathway play essential roles in secondary injury following TBI. Treatment with VPA alleviated TBI-induced secondary brain injury, including neurological deficits, cerebral edema, and neuronal apoptosis. Moreover, VPA treatment upregulated the occurrence of autophagy and Nrf2/ARE pathway activity after TBI, and there was an increase in H3, H4 histone acetylation levels, accompanied by decreased transcriptional activity of the HDAC3 promoter in cortical lesions. These results suggest that VPA-mediated up-regulation of autophagy and antioxidative responses are likely due to increased activation of Nrf2/ARE pathway, through direct inhibition of HDAC3. This inhibition further reduces TBI-induced microglial activation and the subsequent inflammatory response, ultimately leading to neuroprotection.

show abstract

Downregulation of Nrf2 by the combination of TRAIL and Valproic acid induces apoptotic cell death of TRAIL-resistant papillary thyroid cancer cells via suppression of Bcl-xL

Cited by 30 publications

References 44 publications

Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2‐Keap1 interaction: Activation of antioxidative pathway in papillary thyroid carcinoma

Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2‐Keap1 interaction: Activation of antioxidative pathway in papillary thyroid carcinoma

PIN1 Maintains Redox Balance via the c-Myc/NRF2 Axis to Counteract Kras-Induced Mitochondrial Respiratory Injury in Pancreatic Cancer Cells

Valproic Acid Attenuates Traumatic Brain Injury-Induced Inflammation in Vivo: Involvement of Autophagy and the Nrf2/ARE Signaling Pathway

Contact Info

Product

Resources

About