Melanoma in the liver: Oxidative stress and the mechanisms of metastatic cell survival

Obrador, Elena; Salvador, Rosario; López-Blanch, Rafael; Jihad-Jebbar, Ali; Alcácer, Javier; Benlloch, María; Pellicer, José A.; Estrela, José M.

doi:10.1016/j.semcancer.2020.05.001

Cited by 14 publications

(12 citation statements)

References 168 publications

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“…On the other hand, NFE2L2 controls the basal and induced expression of an array of antioxidant response element-dependent genes. By this way, it is involved in the protection of the body against cancer, but at the same time, it is overexpressed in different tumors, thus resulting in a pro-survival phenotype that favors tumor growth and resistance to oxidants and oncotherapy [40].…”

Section: Discussionmentioning

confidence: 99%

Effect of Kaempferol and Its Glycoside Derivatives on Antioxidant Status of HL-60 Cells Treated with Etoposide

et al. 2022

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Kaempferol is a well-known antioxidant found in many plants and plant-based foods. In plants, kaempferol is present mainly in the form of glycoside derivatives. In this work, we focused on determining the effect of kaempferol and its glycoside derivatives on the expression level of genes related to the reduction of oxidative stress—NFE2L2, NQO1, SOD1, SOD2, and HO-1; the enzymatic activity of superoxide dismutases; and the level of glutathione. We used HL-60 acute promyelocytic leukemia cells, which were incubated with the anticancer drug etoposide and kaempferol or one of its three glycoside derivatives isolated from the aerial parts of Lens culinaris Medik.—kaempferol 3-O-[(6-O-E-caffeoyl)-β-d-glucopyranosyl-(1→2)]-β-d-galactopyranoside-7-O-β-d-glucuropyranoside (P2), kaempferol 3-O-[(6-O-E-p-coumaroyl)-β-d-glucopyranosyl-(1→2)]-β-d-galactopyranoside-7-O-β-d-glucuropyranoside (P5), and kaempferol 3-O-[(6-O-E-feruloyl)-β-d-glucopyranosyl-(1→2)]-β-d-galactopyranoside-7-O-β-d-glucuropyranoside (P7). We showed that none of the tested compounds affected NFE2L2 gene expression. Co-incubation with etoposide (1 µM) and kaempferol (10 and 50 µg/mL) leads to an increase in the expression of the HO-1 (9.49 and 9.33-fold at 10 µg/mL and 50 µg/mL, respectively), SOD1 (1.68-fold at 10 µg/mL), SOD2 (1.72-fold at 10–50 µg/mL), and NQO1 (1.84-fold at 50 µg/mL) genes in comparison to cells treated only with etoposide. The effect of kaempferol derivatives on gene expression differs depending on the derivative. All tested polyphenols increased the SOD activity in cells co-incubated with etoposide. We observed that the co-incubation of HL-60 cells with etoposide and kaempferol or derivative P7 increases the level of total glutathione in these cells. Taken together, our observations suggest that the antioxidant activity of kaempferol is related to the activation of antioxidant genes and proteins. Moreover, we observed that glycoside derivatives can have a different effect on the antioxidant cellular systems than kaempferol.

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Section: Discussionmentioning

confidence: 99%

Effect of Kaempferol and Its Glycoside Derivatives on Antioxidant Status of HL-60 Cells Treated with Etoposide

et al. 2022

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“…To further test this postulate, we investigated the effect on astrocyte GSH levels of specific inhibitors of GGT activity (acivicin) [ 34 ], Cys uptake by the ASC transport system for neutral amino acids [(1)-amino(1-(3,5-dichlorophenyl)-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid, ACPP] [ 35 ] or cystine uptake by the Xc - cystine/glutamate antiporter (sulfasalazine, SSZ) [ 36 ]. These are the main carriers of Cys and cystine in mammalian cells (see Obrador [ 37 ]). As shown in Table 7 , GSH depletion in astrocytes is more profound in the presence of specific inhibitors of GGT or ASC-mediated Cys transport.…”

Section: Resultsmentioning

confidence: 99%

“…It has been demonstrated that astrocytes provide Cys to neurons by releasing GSH [ 13 ] via the multi-drug-resistant protein 1 [ 50 ]. Astrocytes can degrade extracellular GSH via GGT and release Cys-Gly, which is broken down by the action of a plasma-membrane-bound dipeptidase [ 37 ]. Then, free Cys, which is rate-limiting for GSH synthesis, can be taken up through the ASC system [ 37 ] ( Table 7 ).…”

Section: Discussionmentioning

confidence: 99%

“…Astrocytes can degrade extracellular GSH via GGT and release Cys-Gly, which is broken down by the action of a plasma-membrane-bound dipeptidase [ 37 ]. Then, free Cys, which is rate-limiting for GSH synthesis, can be taken up through the ASC system [ 37 ] ( Table 7 ). The blood supply of all other amino-acid precursors for GSH synthesis is not limited in ALS mice ( Table 6 A).…”

Section: Discussionmentioning

confidence: 99%

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An Intercellular Flow of Glutathione Regulated by Interleukin 6 Links Astrocytes and the Liver in the Pathophysiology of Amyotrophic Lateral Sclerosis

et al. 2021

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Oxidative stress has been proposed as a major mechanism of damage to motor neurons associated with the progression of amyotrophic lateral sclerosis (ALS). Astrocytes are the most numerous glial cells in the central nervous system and, under physiological conditions, protect neurons from oxidative damage. However, it is uncertain how their reactive phenotype may affect motor neurons during ALS progression. In two different ALS mouse models (SOD1G93A and FUS-R521C), we found that increased levels of proinflammatory interleukin 6 facilitate glutathione (GSH) release from the liver to blood circulation, which can reach the astrocytes and be channeled towards motor neurons as a mechanism of antioxidant protection. Nevertheless, although ALS progression is associated with an increase in GSH efflux from astrocytes, generation of reactive oxygen species also increases, suggesting that as the disease progresses, astrocyte-derived oxidative stress could be key to motor-neuron damage.

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“…The production of large amounts of ROS leads to irreversible damage and the depletion of antioxidant capacity and defense mechanisms of cancer cells. Moreover, one of the therapeutic methods assumes the reduction of the intracellular GSH concentration, which may cause a pro-apoptotic effect in tumor cells [ 9 , 10 , 11 , 12 ]. Due to the lack of efficacious methods of melanoma therapy, a new method of medical care for patients diagnosed with this type of tumor is still needed.…”

Section: Introductionmentioning

confidence: 99%

Ketoprofen Combined with UVA Irradiation Exerts Higher Selectivity in the Mode of Action against Melanotic Melanoma Cells than against Normal Human Melanocytes

Banach

Kowalska

Rzepka

et al. 2021

IJMS

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Malignant melanoma is responsible for the majority of skin cancer-related deaths. The methods of cancer treatment include surgical removal, chemotherapy, immunotherapy, and targeted therapy. However, neither of these methods gives satisfactory results. Therefore, the development of new anticancer therapeutic strategies is very important and may extend the life span of people suffering from melanoma. The aim of this study was to examine the effect of ketoprofen (KTP) and UVA radiation (UVAR) therapy on cell proliferation, apoptosis, and cell cycle distribution in both melanotic melanoma cells (COLO829) and human melanocytes (HEMn-DP) in relation to its supportive effect in the treatment of melanoma. The therapy combining the use of pre-incubation with KTP and UVAR causes a significant increase in the anti-proliferative properties of ketoprofen towards melanoma cells and the co-exposure of melanotic melanoma cells induced apoptosis shown as the mitochondrial membrane breakdown, cell-cycle deregulation, and DNA fragmentation. Moreover, co-treatment led to GSH depletion showing its pro-apoptotic effect dependent on ROS overproduction. The treatment did not show a significant effect on normal cells—melanocytes—which indicates its high selectivity. The results suggest a possible benefit from the use of the ketoprofen and ultraviolet A irradiation as a new concept of melanotic melanoma therapy.

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Melanoma in the liver: Oxidative stress and the mechanisms of metastatic cell survival

Cited by 14 publications

References 168 publications

Effect of Kaempferol and Its Glycoside Derivatives on Antioxidant Status of HL-60 Cells Treated with Etoposide

Effect of Kaempferol and Its Glycoside Derivatives on Antioxidant Status of HL-60 Cells Treated with Etoposide

An Intercellular Flow of Glutathione Regulated by Interleukin 6 Links Astrocytes and the Liver in the Pathophysiology of Amyotrophic Lateral Sclerosis

Ketoprofen Combined with UVA Irradiation Exerts Higher Selectivity in the Mode of Action against Melanotic Melanoma Cells than against Normal Human Melanocytes

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