Role of Nrf2 and mitochondria in cancer stem cells; in carcinogenesis, tumor progression, and chemoresistance

Payandeh, Zahra; Tazehkand, Abbas Pirpour; Barati, Ghasem; Pouremamali, Farhad; Kahroba, Houman; Baradaran, Behzad; Samadi, Nasser

doi:10.1016/j.biochi.2020.09.014

Cited by 38 publications

(16 citation statements)

References 207 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An additional feature of this quite intricate scenario is cell heterogeneity in the bulk cancer; indeed, this permits the coexistence of diverse cell populations. Recent findings have outlined that cancer stem cells (CSCs) may be the pioneers of innate/acquired [ 4 , 5 , 6 ] conferring and spreading a resistance phenotype in the whole cancer pool and to other organs [ 3 , 4 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance

Genovese

Carinci

Modesti

et al. 2021

IJMS

View full text Add to dashboard Cite

Mitochondria are key regulators of cell survival and are involved in a plethora of mechanisms, such as metabolism, Ca2+ signaling, reactive oxygen species (ROS) production, mitophagy and mitochondrial transfer, fusion, and fission (known as mitochondrial dynamics). The tuning of these processes in pathophysiological conditions is fundamental to the balance between cell death and survival. Indeed, ROS overproduction and mitochondrial Ca2+ overload are linked to the induction of apoptosis, while the impairment of mitochondrial dynamics and metabolism can have a double-faceted role in the decision between cell survival and death. Tumorigenesis involves an intricate series of cellular impairments not yet completely clarified, and a further level of complexity is added by the onset of apoptosis resistance mechanisms in cancer cells. In the majority of cases, cancer relapse or lack of responsiveness is related to the emergence of chemoresistance, which may be due to the cooperation of several cellular protection mechanisms, often mitochondria-related. With this review, we aim to critically report the current evidence on the relationship between mitochondria and cancer chemoresistance with a particular focus on the involvement of mitochondrial dynamics, mitochondrial Ca2+ signaling, oxidative stress, and metabolism to possibly identify new approaches or targets for overcoming cancer resistance.

show abstract

Section: Introductionmentioning

confidence: 99%

Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance

Genovese

Carinci

Modesti

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Oxaliplatin resistance is a common phenomenon in the failure of treatment following the surgery 2 . Nuclear factor− erythroid 2−related factor 2 (Nrf2) plays a key role in the protection of cells against oxidative stress and inflammation in numerous tissues 3 and its role has been investigated in cancer stem cells 4,5 .…”

Section: Introductionmentioning

confidence: 99%

The Impact of Nrf2 Silencing on Nrf2-PD-L1 Axis to Overcome Oxaliplatin Resistance and Migration in Colon Cancer Cells

Payandeh¹,

Tazehkand²,

Mansoori³

et al. 2021

AJMB

Self Cite

View full text Add to dashboard Cite

Background: Nuclear factor-erythroid 2-related factor 2 (Nrf2) plays a key role in promoting chemoresistance in various cancers. PD-L1 is one of the downstream targets of the Nrf2 signaling pathway. This molecule has some beneficial impacts on tumors growth by inhibition of the immune system. This study aimed to investigate the potential role of the Nrf2-PD-L1 axis in the promotion of oxaliplatin resistance in colon cancer cells. Methods: We examined Nrf2, PD- L1, and CD80 expression in the tumor and margin tissue samples from CRC patients. After that role of the Nrf2-PD-L1 axis in promotion of Oxaliplatin resistance was investigated. Results: Our data revealed that Nrf2 and PD-L1 mRNA expressions were markedly higher in tumor tissues compared to margin tissues. The PD-L1 mRNA expression level was also increased in the resistant cells. However, Nrf2 expression was decreased in SW480/Res cells and increased in LS174T/Res cells. The inhibition of Nrf2 through siRNA treatment in SW480/Res and LS174T/Res cells has decreased the IC50 values of oxaliplatin. Inhibition of the Nrf2 has significantly increased the oxaliplatin-induced apoptosis, and reduced the migration in SW480/Res cells. Conclusion: It is suggested that effective inhibition of Nrf2-PD-L1 signaling pathways can be considered as a novel approach to improve oxaliplatin efficacy in colon cancer patients.

show abstract

“…Oxidative imbalance is accompanied by the reduced activity of nuclear-related factor 2 (Nrf2) in the body, while NRF2 is a well-known transcriptional master regulator, which is believed to recognize cellular oxidative stress, and then combine with the promoters of cytoprotective and antioxidant genes to promote antioxidant reactions which participate in maintaining the redox state of cells. 44 In addition, as an upstream and downstream regulator, Nrf2 can regulate the transcription of anti-oxidative stress and anti-inflammatory genes, and its activation is one of the main defense mechanisms of cells. 45 The up-regulated Nrf2 signaling pathway inhibits the release of pro-inflammatory cytokines COX-2, IL-6, and TNF-α, improves liver immunity and metabolism, and reduces inflammatory injury and hypofunction.…”

mentioning

confidence: 99%

Taxifolin, Extracted from Waste Larix olgensis Roots, Attenuates CCl4-Induced Liver Fibrosis by Regulating the PI3K/AKT/mTOR and TGF-β1/Smads Signaling Pathways

Liu¹,

Liu²,

Ding³

et al. 2021

DDDT

View full text Add to dashboard Cite

Purpose Taxifolin is a kind of dihydroflavone and is usually used as a food additive and health food for its antioxidant, anti-inflammatory, and anti-tumor activities. The purpose of this research is to probe into the hepatoprotective activity and the molecular mechanism of taxifolin. Materials and Methods The liver fibrosis model was established by intraperitoneal injection of 5 mL/kg body weight of CCl 4 (20% CCl 4 peanut oil solution), and taxifolin was dissolved with 0.9% physiological saline and administered intragastrically to mice. Results The results indicated that CCl 4 -induced significantly increased the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice. Histopathological examination showed severe hepatocyte necrosis and hepatic tissue lesion. Immunohistochemical staining and rt-PCR analysis demonstrated that the expressions of inducible nitric oxide synthetase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, IL-6, and TNF-α were increased. These changes were significantly reversed when treated with taxifolin. In addition, TUNEL staining and Bcl-2/Bax pathway confirmed that taxifolin significantly inhibited hepatocyte apoptosis. Besides, the research confirmed that taxifolin also inhibited the activation of hepatic stellate cells and the production of extracellular matrix (ECM) by regulating PI3K/AKT/mTOR and TGF-β1/Smads pathways. Conclusion Taxifolin inhibited inflammation, and attenuated CCl 4 -induced oxidative stress and cell apoptosis by regulating PI3K/AKT/mTOR and TGF-β1/Smads pathways, which might in part contributed to taxifolin anti-hepatic fibrosis, further demonstrating that taxifolin may be an efficient hepatoprotective agent.

show abstract

Role of Nrf2 and mitochondria in cancer stem cells; in carcinogenesis, tumor progression, and chemoresistance

Cited by 38 publications

References 207 publications

Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance

Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance

The Impact of Nrf2 Silencing on Nrf2-PD-L1 Axis to Overcome Oxaliplatin Resistance and Migration in Colon Cancer Cells

Taxifolin, Extracted from Waste Larix olgensis Roots, Attenuates CCl4-Induced Liver Fibrosis by Regulating the PI3K/AKT/mTOR and TGF-β1/Smads Signaling Pathways

Contact Info

Product

Resources

About