Role of Natural and Synthetic Compounds in Modulating NRF2/KEAP1 Signaling Pathway in Prostate Cancer

Tossetta, Giovanni; Fantone, Sonia; Marzioni, Daniela; Mazzucchelli, Roberta

doi:10.3390/cancers15113037

Cited by 20 publications

(10 citation statements)

References 189 publications

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“…Therefore, scavenging ROS and breaking the redox equilibrium in cancer cells might be an approach for cancer treatment. Nuclear factor erythroid 2-related factor 2 (NRF2), a nuclear transcription factor, plays a pivotal role in the development of several non-cancerous and cancerous diseases [12][13][14][15][16] through relieving intracellular ROS via the activation of target genes (NADPH, HO-1, NQO1, etc.) [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Paradox: Curcumin, a Natural Antioxidant, Suppresses Osteosarcoma Cells via Excessive Reactive Oxygen Species

Wang

Zandieh-Doulabi

et al. 2023

IJMS

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Osteosarcoma (OS) is an aggressive tumor with a rare incidence. Extended surgical resections are the prevalent treatment for OS, which may cause critical-size bone defects. These bone defects lead to dysfunction, weakening the post-surgical quality of patients’ life. Hence, an ideal therapeutic agent for OS should simultaneously possess anti-cancer and bone repair capacities. Curcumin (CUR) has been reported in OS therapy and bone regeneration. However, it is not clear how CUR suppresses OS development. Conventionally, CUR is considered a natural antioxidant in line with its capacity to promote the nuclear translocation of a nuclear transcription factor, nuclear factor erythroid 2 (NRF2). After nuclear translocation, NRF2 can activate the transcription of some antioxidases, thereby circumventing excess reactive oxygen species (ROS) that are deleterious to cells. Intriguingly, this research demonstrated that, in vitro, 10 and 20 μM CUR increased the intracellular ROS in MG-63 cells, damaged cells’ DNA, and finally caused apoptosis of MG-63 cells, although increased NRF2 protein level and the expression of NRF2-regulated antioxidase genes were identified in those two groups.

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Section: Introductionmentioning

confidence: 99%

Paradox: Curcumin, a Natural Antioxidant, Suppresses Osteosarcoma Cells via Excessive Reactive Oxygen Species

Wang

Zandieh-Doulabi

et al. 2023

IJMS

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“…In addition, these drugs also increased cellular levels of reduced GSH, a major cellular antioxidant in both neuronal and nonneuronal cells. GSH reacts with ROS to lower their amounts, and helps maintain acceptable levels of oxidative stress [ 47 , 48 , 49 ]. GSH acts alone or in conjunction with enzymes to reduce superoxide and hydroxyl radicals and peroxynitrites generated during normal cellular metabolism and is a preferred substrate for several enzymes involved in antioxidant protection and xenobiotic metabolism [ 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Opioids Alleviate Oxidative Stress via the Nrf2/HO-1 Pathway in LPS-Stimulated Microglia

Mali

Honc

Hejnova

et al. 2023

IJMS

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Opioids are known to have antioxidant effects and to modulate microglial function under certain conditions. It has been previously shown that opioid ligands can effectively inhibit the release of proinflammatory cytokines when stimulated with lipopolysaccharide (LPS) and convert microglia to an anti-inflammatory polarization state. Here, we used C8-B4 cells, the mouse microglial cell line activated by LPS as a model to investigate the anti-inflammatory/antioxidant potential of selected opioid receptor agonists (DAMGO, DADLE, and U-50488). We found that all of these ligands could exert cytoprotective effects through the mechanism affecting LPS-induced ROS production, NADPH synthesis, and glucose uptake. Interestingly, opioids elevated the level of reduced glutathione, increased ATP content, and enhanced mitochondrial respiration in microglial cells exposed to LPS. These beneficial effects were associated with the upregulation of the Nrf2/HO-1 pathway. The present results indicate that activation of opioid signaling supports the preservation of mitochondrial function with concomitant elimination of ROS in microglia and suggest that an Nrf2/HO-1 signaling pathway-dependent mechanism is involved in the antioxidant efficacy of opioids. Opioid receptor agonists may therefore be considered as agents to suppress oxidative stress and inflammatory responses of microglia.

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“…Natural and synthetic compounds are widely used to treat several cancerous and noncancerous diseases [ 34 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. Both these types of compounds can be used alone or in combination with chemotherapy to improve treatment outcomes or counteract the side effects of chemo- and radiotherapy in several types of cancers, including ovarian cancer.…”

Section: Slc7a11 Modulation By Natural and Synthetic Compounds In Ova...mentioning

confidence: 99%

Role of SLC7A11/xCT in Ovarian Cancer

Fantone,

Piani,

Olivieri

et al. 2024

IJMS

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Ovarian cancer is one of the most dangerous gynecologic cancers worldwide and has a high fatality rate due to diagnosis at an advanced stage of the disease as well as a high recurrence rate due to the occurrence of chemotherapy resistance. In fact, chemoresistance weakens the therapeutic effects, worsening the outcome of this pathology. Solute Carrier Family 7 Member 11 (SLC7A11, also known as xCT) is the functional subunit of the Xc− system, an anionic L-cystine/L-glutamate antiporter expressed on the cell surface. SLC7A11 expression is significantly upregulated in several types of cancers in which it can inhibit ferroptosis and favor cancer cell proliferation, invasion and chemoresistance. SLC7A11 expression is also increased in ovarian cancer tissues, suggesting a possible role of this protein as a therapeutic target. In this review, we provide an overview of the current literature regarding the role of SLC7A11 in ovarian cancer to provide new insights on SLC7A11 modulation and evaluate the potential role of SLC7A11 as a therapeutic target.

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Role of Natural and Synthetic Compounds in Modulating NRF2/KEAP1 Signaling Pathway in Prostate Cancer

Cited by 20 publications

References 189 publications

Paradox: Curcumin, a Natural Antioxidant, Suppresses Osteosarcoma Cells via Excessive Reactive Oxygen Species

Paradox: Curcumin, a Natural Antioxidant, Suppresses Osteosarcoma Cells via Excessive Reactive Oxygen Species

Opioids Alleviate Oxidative Stress via the Nrf2/HO-1 Pathway in LPS-Stimulated Microglia

Role of SLC7A11/xCT in Ovarian Cancer

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