Curcumin Activates the Nrf2 Pathway and Induces Cellular Protection Against Oxidative Injury

Ashrafizadeh, Milad; Ahmadi, Zahra; Mohammadinejad, Reza; Farkhondeh, Tahereh; Samarghandian, Saeed

doi:10.2174/1566524019666191016150757

Cited by 96 publications

(65 citation statements)

References 128 publications

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“…Many preclinical studies have highlighted the benefit of phytochemical compounds as anticancer agents, especially in combination with conventional anticancer drugs [27]. However, the use of the zinc-curcumin complex as an antitumor metal-based drug can face some limitations, since curcumin has been shown to induce NRF2 [28], as also demonstrated by our previous findings [13,29], and to reduce cancer cell death. Indeed, NRF2 overexpression could play a cytoprotective role in cancer cells, regardless of p53 activation, which is one reason why the NRF2 pathway could be depicted as a molecular vulnerability to be therapeutically exploited.…”

Section: Introductionmentioning

confidence: 65%

p62/SQSTM1/Keap1/NRF2 Axis Reduces Cancer Cells Death-Sensitivity in Response to Zn(II)–Curcumin Complex

et al. 2021

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The hyperactivation of nuclear factor erythroid 2 p45-related factor 2 (NRF2), frequently found in many tumor types, can be responsible for cancer resistance to therapies and poor patient prognosis. Curcumin has been shown to activate NRF2 that has cytotprotective or protumorigenic roles according to tumor stage. The present study aimed at investigating whether the zinc–curcumin Zn(II)–curc compound, which we previously showed to display anticancer effects through multiple mechanisms, could induce NRF2 activation and to explore the underlying molecular mechanisms. Biochemical studies showed that Zn(II)–curc treatment increased the NRF2 protein levels along with its targets, heme oxygenase-1 (HO-1) and p62/SQSTM1, while markedly reduced the levels of Keap1 (Kelch-like ECH-associated protein 1), the NRF2 inhibitor, in the cancer cell lines analyzed. The silencing of either NRF2 or p62/SQSTM1 with specific siRNA demonstrated the crosstalk between the two molecules and that the knockdown of either molecule increased the cancer cell sensitivity to Zn(II)–curc-induced cell death. This suggests that the crosstalk between p62/SQSTM1 and NRF2 could be therapeutically exploited to increase cancer patient response to therapies.

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Section: Introductionmentioning

confidence: 65%

p62/SQSTM1/Keap1/NRF2 Axis Reduces Cancer Cells Death-Sensitivity in Response to Zn(II)–Curcumin Complex

et al. 2021

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“…Liu et al [13] indicated JH could lead to cell apoptosis in ovarian cancer cell lines SK-OV-3 by inhibiting the AKT/mTOR pathway by using an MTT assay. Ashra zadeh et al [13] found that JH possess various effects including antioxidant, antibacterial, antineoplastic and anti-in ammatory via targeting the Nrf2 signaling pathway. There are reports that show Chuanxiong (Ligusticum chuanxiong) and Danggui (Angelica sinensis) also can exert anti-tumor effects.…”

Section: Discussionmentioning

confidence: 99%

System Pharmacological Mechanism and Compatibility Laws of Jianghuang from Traditional Chinese Medicine In Blood-Regulating Formulae

Liu¹,

Wang

2020

Preprint

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Background: Jianghuang (JH) is a popular ingredient in blood-regulating traditional Chinese Medicine (TCM) that could be effective for the treatment of various diseases. We demonstrate the compatibility laws and system pharmacological mechanisms of the key formula containing JH by leveraging data mining of bioinformatics databases.Material/Methods: The compatibility laws of blood-regulating formulae containing JH from the Chinese Traditional Medicine Formula Dictionary were analyzed using a generalized rule induction (GRI) algorithm implemented. The putative target gene and miRNA were retrieved via a combination of the Arrowsmith knowledge discovery tool and FunRich 3.1.3. System pharmacological mechanisms are traced by their protein-protein interaction (PPI) network, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted using Uniprot, the Human Protein Atlas (HPA), STRING 11.0, and KOBAS 3.0.Results: We found that the JH-CX-DG formula (Ligusticum chuanxiong-Angelica sinensis) could represent a key formula containing JH in blood-regulating TCM formulae. The JH-CX-DG formula was observed to directly target AKT, TLR4, caspase-3, PI3K, mTOR, p38 MAPK, VEGF, iNOS, Nrf2, BDNF, NF-κB, Bcl-2, and Bax 13 targets and regulate targets through 13 miRNA. The PPI network and KEGG pathway enrichment analysis showed that the JH-CX-DG formula possess potential pharmacological effects including anti-inflammatory, improving microcirculation, and anti-tumor through the regulation of multiple pathways including PI3K/Akt, MAPK, Toll-like receptor, T cell receptor, EGFR, VEGFR, Apoptosis, HIF-1 (p < 0.05).Conclusion: The JH-CX-DG formula can exert beneficial pharmacological effects through multi-target and multi-pathway interactions. It can be effectively administered for the treatment of inflammatory diseases, microcirculation disorders, cardiovascular disease, and cancer. We found a new effective drug formula through analyzing the compatibility law and systemic pharmacological mechanism of JH. Our study provides a theoretical basis and directions for subsequent research on the JH-CX-DG formula.

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“…Nrf2 is a transcription factor that regulates the expression of genes that have antioxidant response element-like sequences in their promoter to antioxidant and reactive oxygen species (ROS) detoxification [ 17 ] such as heme oxygenase-1 (HO1), peroxiredoxins, and glutamate-cysteine ligase (GCL) [ 18 , 19 , 20 , 21 , 22 , 23 ]. Nrf2 protects normal cells against DNA damage induced by ROS and malignant cells against chemotherapy [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Roles of Nrf2 in Gastric Cancer: Targeting for Therapeutic Strategies

et al. 2021

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Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) is a specific transcription factor with potent effects on the regulation of antioxidant gene expression that modulates cell hemostasis under various conditions in tissues. However, the effects of Nrf2 on gastric cancer (GC) are not fully elucidated and understood. Evidence suggests that uncontrolled Nrf2 expression and activation has been observed more frequently in malignant tumors, including GC cells, which is then associated with increased antioxidant capacity, chemoresistance, and poor clinical prognosis. Moreover, Nrf2 inhibitors and the associated modulation of tumor cell redox balance have shown that Nrf2 also has beneficial effects on the therapy of various cancers, including GC. Based on previous findings on the important role of Nrf2 in GC therapy, it is of great interest to scientists in basic and clinical tumor research that Nrf2 can be active as both an oncogene and a tumor suppressor depending on different background situations.

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Curcumin Activates the Nrf2 Pathway and Induces Cellular Protection Against Oxidative Injury

Cited by 96 publications

References 128 publications

p62/SQSTM1/Keap1/NRF2 Axis Reduces Cancer Cells Death-Sensitivity in Response to Zn(II)–Curcumin Complex

p62/SQSTM1/Keap1/NRF2 Axis Reduces Cancer Cells Death-Sensitivity in Response to Zn(II)–Curcumin Complex

System Pharmacological Mechanism and Compatibility Laws of Jianghuang from Traditional Chinese Medicine In Blood-Regulating Formulae

Roles of Nrf2 in Gastric Cancer: Targeting for Therapeutic Strategies

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