The mechanistic insights of the antioxidant Keap1-Nrf2 pathway in oncogenesis: a deadly scenario

Mukherjee, Anirban Goutam; Gopalakrishnan, Abilash Valsala

doi:10.1007/s12032-023-02124-4

Cited by 8 publications

(2 citation statements)

References 286 publications

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“…In contrast, methylation of the KEAP1 promoter has been found to reduce KEAP1 levels in lung cancer, a process that is associated with elevated NRF2 expression [22]. NRF2 upregulation in cancer and its role in promoting chemoresistance are influenced by a combination of transcriptional, translational, and epigenetic modifications [31]. However, the specific mechanisms driving these alterations in various cancer types require further investigation.…”

Section: Discussionmentioning

confidence: 99%

Deferasirox Causes Leukaemia Cell Death through Nrf2-Induced Ferroptosis

Hsu,

Wang,

Lin

et al. 2024

Antioxidants

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Acute lymphoblastic leukaemia (ALL) is the most prevalent cancer in children, and excessive iron buildup resulting from blood transfusions and chemotherapy potentially has a negative impact on treatment outcomes and prognosis in patients with ALL. Therefore, initiating early iron chelation therapy during ALL treatment is a logical approach. Ideally, the selected iron chelator should also possess anti-leukaemia properties. The aim of the present study was to explore the potential impact and underlying mechanism of deferasirox (DFX) in ALL therapy. This study proved that DFX, an iron chelator, is capable of inducing leukaemia cell death through ferroptosis, which is achievable by increasing the expression of acetylated nuclear factor erythroid 2-related factor 2 (NRF2). More specifically, NRF2 acetylation on Lys599 was facilitated by acetyltransferase-p300/CBP. These findings indicate that DFX could serve as a potent adjunctive medication for patients with ALL. Moreover, DFX may offer dual benefits in ALL treatment, functioning as both an iron chelator and NRF2-modulating agent. Further research and clinical trials are necessary to fully elucidate the therapeutic potential of DFX in patients with ALL and incorporate it into treatment protocols.

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Section: Discussionmentioning

confidence: 99%

Deferasirox Causes Leukaemia Cell Death through Nrf2-Induced Ferroptosis

Hsu,

Wang,

Lin

et al. 2024

Antioxidants

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“…However, CSCs exhibit a low level of ROS via the upregulation of cellular defense proteins, such as Nrf2 ( Xue et al ., 2020 ). After dissociating from Keap1, Nrf2 translocates into the nucleus and upregulates antioxidant enzymes, including heme oxygenase-1, catalase, and superoxide dismutase-2, through the regulation of antioxidant response elements ( Xue et al ., 2020 ; Mukherjee and Gopalakrishnan, 2023 ). The upregulation of CD44 expression in CSCs mediates p62-associated Nrf2 activation followed by the autophagic degradation of Keap1 ( Ryoo et al ., 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Cordycepin Enhanced Therapeutic Potential of Gemcitabine against Cholangiocarcinoma via Downregulating Cancer Stem-Like Properties

Lee,

Na,

Seong

et al. 2024

Biomol Ther (Seoul)

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Cordycepin, a valuable bioactive component isolated from Cordyceps militaris , has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine co-treatment reduced the CD44 high CD133 high population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2–related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.

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Calcium (Ca²⁺) hemostasis, mitochondria, autophagy, and mitophagy contribute to Alzheimer's disease as early moderators

Hadi,

Mortaja,

Hadi

2024

Cell Biochemistry & Function

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This review rigorously investigates the early cerebral changes associated with Alzheimer's disease, which manifest long before clinical symptoms arise. It presents evidence that the dysregulation of calcium (Ca2+) homeostasis, along with mitochondrial dysfunction and aberrant autophagic processes, may drive the disease's progression during its asymptomatic, preclinical stage. Understanding the intricate molecular interplay that unfolds during this critical period offers a window into identifying novel therapeutic targets, thereby advancing the treatment of neurodegenerative disorders. The review delves into both established and emerging insights into the molecular alterations precipitated by the disruption of Ca2+ balance, setting the stage for cognitive decline and neurodegeneration.

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The mechanistic insights of the antioxidant Keap1-Nrf2 pathway in oncogenesis: a deadly scenario

Cited by 8 publications

References 286 publications

Deferasirox Causes Leukaemia Cell Death through Nrf2-Induced Ferroptosis

Deferasirox Causes Leukaemia Cell Death through Nrf2-Induced Ferroptosis

Cordycepin Enhanced Therapeutic Potential of Gemcitabine against Cholangiocarcinoma via Downregulating Cancer Stem-Like Properties

Calcium (Ca²⁺) hemostasis, mitochondria, autophagy, and mitophagy contribute to Alzheimer's disease as early moderators

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The mechanistic insights of the antioxidant Keap1-Nrf2 pathway in oncogenesis: a deadly scenario

Cited by 8 publications

References 286 publications

Deferasirox Causes Leukaemia Cell Death through Nrf2-Induced Ferroptosis

Deferasirox Causes Leukaemia Cell Death through Nrf2-Induced Ferroptosis

Cordycepin Enhanced Therapeutic Potential of Gemcitabine against Cholangiocarcinoma via Downregulating Cancer Stem-Like Properties

Calcium (Ca2+) hemostasis, mitochondria, autophagy, and mitophagy contribute to Alzheimer's disease as early moderators

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Product

Resources

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Calcium (Ca²⁺) hemostasis, mitochondria, autophagy, and mitophagy contribute to Alzheimer's disease as early moderators