Estrogen increases Nrf2 activity through activation of the PI3K pathway in MCF-7 breast cancer cells

Wu, Juanjuan; Williams, Devin; Walter, Grant A.; Thompson, Winston E.; Sidell, Neil

doi:10.1016/j.yexcr.2014.08.030

Cited by 70 publications

(54 citation statements)

References 58 publications

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“…Amandla demonstrated the beneficial effects of Nrf2-activating agents on kidney injury[26]. Juanjuan Wua also reported that the activation of the PI3K/Akt signaling pathway could increase Nrf2 activity[27]. In this study, the expression of Nrf2 and the activity of the PI3K/Akt signaling pathway were significantly increased in ZWT-treated kidneys compared to those in untreated CIS-injured kidneys.…”

Section: Discussionsupporting

confidence: 49%

The protective effects of Zhen-Wu-Tang against cisplatin-induced acute kidney injury in rats

Liu

Shou-yu

et al. 2017

PLoS ONE

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Acute kidney injury (AKI) is a common clinical condition that confers a risk of progression of chronic kidney disease and a high risk of death. The purpose of the current study is to investigate the anti-apoptotic and anti-fibrotic effects of Zhen-Wu-Tang (ZWT) on cisplatin (CIS)-induced renal injury and elucidate the involvement of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the PI3K/Akt signaling pathway, transforming growth factor (TGF)-β and the Wnt/β-catenin signaling pathway in the positive effects of Zhen-Wu-Tang on the kidneys. Wistar rats were randomly assigned into six groups of 6 rats each as follows: normal control 1; normal control 2; CIS 1 and CIS 2, which received single intraperitoneal injections of CIS (6 mg/kg); CIS+ZWT 4 and CIS+ZWT 10, which received ZWT (1 ml/100 g/day, ig) starting days after the CIS injection for 4 and 10 days, respectively. Hematoxylin-eosin (H&E) staining was performed to identify the amelioration of histopathological changes in the kidneys and apoptosis of the renal proximal tubular cells. Picrosirius red staining was used to evaluate renal fibrosis after ZWT treatment. The relationship between ZWT and the upregulation of Nrf2, phosphorylation of Akt, and the downregulation of TGF-β and WNT/β-catenin were determined by Western blotting. At the end of the experiment, serum was isolated from the orbital blood of rats, and blood urea nitrogen (BUN) and creatinine (Cr) levels were measured. The results showed that ZWT restored the histological alterations, aberrant collagen deposition in the kidneys and the BUN and Cr levels that were increased by CIS. Treatment with ZWT reduced the expression levels of TGF-β and Wnt and increased the expression levels of Nrf2, PI3K and Akt in the CIS-exposed kidney tissues. Furthermore, ZWT downregulated apoptosis and fibrosis by modulating the expression levels of caspase-3, Bax and alpha-smooth muscle actin (α-SMA). In conclusion, this study provides evidence for the anti-fibrotic and anti-apoptotic roles of ZWT in CIS-induced experimental kidney injury.

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Section: Discussionsupporting

confidence: 49%

The protective effects of Zhen-Wu-Tang against cisplatin-induced acute kidney injury in rats

Liu

Shou-yu

et al. 2017

PLoS ONE

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“…As seen above for O2°− production and thiols, higher SOD and GPx activities appeared in females due to oestrogenic hormones (Borrás et al, 2010;Wu et al, 2014).…”

Section: Liver Oxidative Statussupporting

confidence: 56%

Assessment of potential toxicological aspects of dietary exposure to silicon-rich spirulina in rats

Vidé

Romain

Feillet‐Coudray

et al. 2015

Food and Chemical Toxicology

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Silicon has beneficial effects especially on bones and skin and is important in cardiovascular pathophysiology. Furthermore, in spontaneously hypertensive rats, it reduces hypertension and increases antihypertensive and antiatherogenic gene expressions in the aorta. Thus, incorporating silicon into spirulina could be a way to produce a bioavailable food supplement. The potential toxic effects of silicon-rich spirulina (SES) through haematological and biochemical parameters and inflammatory and oxidative status were evaluated in rats' blood and liver tissue. The study consisted in a 90-day experiment on female and male rats supplemented with three doses (28.5, 57 and 285 mg/kg BW/day) of SES. No mortality, abnormal clinical signs, behavioural changes or macroscopic findings were observed whatever the groups. Haematological parameters were not modified in SES treated-groups. No marked change was recorded in biochemical parameters The liver endogenous antioxidant enzymes (SOD, GPx, catalase) activities were not modified whatever the gender and the dose, just as markers of oxidative stress (O2°(-), TBARS, thiols) and inflammation such as IL-6 and TNF-alpha. Our findings indicate that dietary supplementation of silicon-rich spirulina on rats has no harmful side nor toxic effects and could be beneficial especially in the case of suspicion or installation of pathologies due to oxidative stress.

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“…Nrf2 regulates a number of metabolic pathways, including the induction of antioxidant pathways including the glutathione pathway, as well as NADPH production through G6PD , the rate-limiting enzyme in the pentose phosphate pathway (52). Thus, the observed reduction in MRP1, NRF2 and its downstream effector glutathione reductase due to MCAM knockdown suggests that MCAM works in concert with altered Nrf2 activation, a notion that is supported by the observation that activation of the PI3K/AKT pathway promotes Nrf2 activation in other cancer types (53). In the present study, comparison of the proteome of chemoresistant to other SCLC cell lines revealed perturbations in various metabolic pathways, highlighted by dysregulation of mitochondrial function, gluconeogenesis, glycolysis, and the pentose phosphate pathway.…”

Section: Discussionmentioning

confidence: 87%

MCAM Mediates Chemoresistance in Small-Cell Lung Cancer via the PI3K/AKT/SOX2 Signaling Pathway

et al. 2017

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Despite favorable responses to initial therapy, SCLC relapse occurs within a year exhibiting a multidrug resistant phenotype. Due to limited accessibility of patient tissues for research purpose, SCLC patient derived xenografts (PDXs) have provided the best opportunity to address this limitation. We sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines that exhibited a mesenchymal phenotype and in chemoresistant PDXs compared to matched treatment-naïve tumors. MCAM is a cell membrane protein whose expression has been implicated in multiple human cancers. MCAM expression is also detected in lung adenocarcinoma; however, its expression and role in SCLC is has not been explored. MCAM knockdown in chemoresistant cells reduced cell proliferation and decreased the IC50 inhibitory concentration of chemotherapeutic drugs. MCAM was found to modulate sensitivity of SCLC cells to chemotherapeutic drugs through up-regulation of MRP1/ABCC1 expression and of the PI3/AKT pathway in a SOX2-dependent manner. Metabolomic profiling revealed that MCAM modulates lactate production in chemoresistant cells that exhibit a distinct metabolic phenotype characterized by low oxidative phosphorylation. MCAM may serve as a novel therapeutic target to overcome chemoresistance in SCLC.

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Estrogen increases Nrf2 activity through activation of the PI3K pathway in MCF-7 breast cancer cells

Cited by 70 publications

References 58 publications

The protective effects of Zhen-Wu-Tang against cisplatin-induced acute kidney injury in rats

The protective effects of Zhen-Wu-Tang against cisplatin-induced acute kidney injury in rats

Assessment of potential toxicological aspects of dietary exposure to silicon-rich spirulina in rats

MCAM Mediates Chemoresistance in Small-Cell Lung Cancer via the PI3K/AKT/SOX2 Signaling Pathway

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