Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Cancers, Journal Year: 2024, Volume and Issue: 16(12), P. 2262 - 2262

Published: June 18, 2024

Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and high mortality rate. This review discusses etiologic risk factors for melanoma, diagnostic prognostic tools, including recent advances in molecular biology, omics, bioinformatics, provides an overview its therapy. Since the incidence melanoma rising remains unacceptably high, we discuss inherent properties, melanogenesis, that make this disease resilient treatment propose use AI solve above complex multidimensional problems. We provide on vitamin D anticancerogenic report field can solutions prevention and/or therapy melanoma. Experimental papers clinicopathological studies role status signaling pathways initiated active metabolites prognosis are reviewed. conclude signaling, defined specific nuclear receptors selective activation hydroxyderivatives, benefit new or existing therapeutic approaches. target with computational biology tools solution problem.

Language: Английский

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Lamivudine, Doravirine, and Cabotegravir Downregulate the Expression of Human Endogenous Retroviruses (HERVs), Inhibit Cell Growth, and Reduce Invasive Capability in Melanoma Cell Lines

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1615 - 1615

Published: Jan. 28, 2024

This study explores the impact of antiretroviral administration on expression human endogenous retroviruses (HERVs), cell growth, and invasive capability melanoma lines in culture. We investigated three antiretrovirals-lamivudine, doravirine, cabotegravir-in A375, FO-1, SK-Mel-28, BRAF-mutated, MeWo, P53-mutated, lines. The findings indicate a general these drugs to downregulate HERV-K Pol Env genes hinder viability, mobility, colony formation capacity cells. also demonstrate selectivity against malignant cells, sparing normal epithelial melanocytes. reveals that integrase inhibitor cabotegravir is particularly effective inhibiting growth invasion across different comparison with lamivudine which are inhibitors viral reverse transcriptase enzyme. investigation further delves into molecular mechanisms underlying observed effects, highlighting potential induction ferroptosis, apoptosis, alterations cycle regulatory proteins. Our showed cytostatic effects principally revealed SK-Mel-28 through downregulation retinoblastoma protein phosphorylation and/or cyclin D1 expression. Signs ferroptosis were detected both A375 cells FO-1 by decrease glutathione peroxidase 4 ferritin expression, as well an increase transferrin levels. Apoptosis was but only treatment. Moreover, we explored activity stimulator interferon (STING) its correlation programmed death-ligand 1 (PD-L1) Both STING PD-L1 decreased, suggesting treatments may counteract detrimental activation STING/interferon pathway triggered HERV-K. Finally, this underscores therapeutic significance raise prospect using potentially enhancing responses immune checkpoint inhibitors.

Language: Английский

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Gastric cancer secreted miR-214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Journal Year: 2024, Volume and Issue: 32(3), P. 489 - 502

Published: Jan. 1, 2024

Different from necrosis, apoptosis, autophagy and other forms of cell death, ferroptosis is a mechanism that catalyzes lipid peroxidation polyunsaturated fatty acids under the action iron divalent or lipoxygenase, leading to death.Apatinib currently used in third-line standard treatment advanced gastric cancer, targeting anti-angiogenesis pathway.However, Apatinib-mediated vascular endothelial cells has not been reported yet.Tumor-secreted exosomes can be taken up into target regulate tumor development, but related yet discovered.Here, we show secreted by cancer carry miR-214-3p directly zinc finger protein A20 negatively ACSL4, key enzyme during ferroptosis, thereby inhibiting reducing efficiency Apatinib.In conclusion, inhibition increase sensitivity Apatinib, promoting antiangiogenic effect suggesting potential combination therapy for cancer.

Language: Английский

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Second-generation BRAF inhibitor Encorafenib resistance is regulated by NCOA4-mediated iron trafficking in the drug-resistant malignant melanoma cells

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 18, 2025

The current study established the first in vitro Encorafenib resistance protocol BRAF-mutated malignant melanoma (MM) cells and investigated resistance-related mechanisms. After establishing Encorafenib-resistant A375-MM cells, resistant-related mechanisms were using WST-1, Annexin V, cell cycle, morphological analysis, live-cell, Western blot, RNA-Seq, transmission electron microscopy-(TEM), oxidative stress iron colorimetric assay. most resistant group, called A375-R, was determined treated with a constant dose of 10 nM over 3 months. viability, apoptosis, G0/G1 arrest reflected acquired chemoresistance. Autophagic Beclin LC3 proteins, AKT signaling increased A375-R. RNA-Seq results also exhibited altered epigenetic regulation resistance; particularly ferritin family members, ion transport pathways. Then, NCOA4, FTH1, levels detected A375-R suggest that metabolism-related mechanism, such as ferritinophagy, might be triggered, which supported by TEM analysis. Iron storage, transport, ferritinophagy have promising potential to targeted for combining BRAF-targeted therapy reverse MM. Moreover, this is evaluating mechanisms, we our findings contribute improving new drug combinations targeting BRAF metabolism different MM cells.

Language: Английский

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Poly-Unsaturated Fatty Acids (PUFAs) from Cunninghamella elegans Grown on Glycerol Induce Cell Death and Increase Intracellular Reactive Oxygen Species

Journal of Fungi, Journal Year: 2024, Volume and Issue: 10(2), P. 130 - 130

Published: Feb. 4, 2024

Cunninghamella elegans NRRL-1393 is an oleaginous fungus able to synthesize and accumulate unsaturated fatty acids, amongst which the bioactive gamma-linolenic acid (GLA) has potential anti-cancer activities. C. was cultured in shake-flask nitrogen-limited media with either glycerol or glucose (both at ≈60 g/L) employed as sole substrate. The assimilation rate of both substrates similar, total biomass production reached 13.0–13.5 g/L, c. 350 h after inoculation (for instances, 27–29 g/L substrate were consumed). Lipid slightly higher on glycerol-based media, compared growth (≈8.4 vs. ≈7.0 g/L). Lipids from grown glycerol, containing 9.5% w/w GLA, transformed into lithium salts (FALS), their effects assessed human normal cancerous cell lines. FALS exhibited cytotoxic within a 48 interval IC50 about 60 μg/mL. Additionally, suppression migration shown, significant elevation oxidative stress levels, induction death. Elementary differences between cancer cells not indicating generic mode action; however, level augmentation may increase susceptibility anticancer drugs, improving chemotherapy effectiveness.

Language: Английский

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Pharmacologically inducing anoikis offers novel therapeutic opportunities in hepatocellular carcinoma

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116878 - 116878

Published: June 5, 2024

Tumor metastasis occurs in hepatocellular carcinoma (HCC), leading to tumor progression and therapeutic failure. Anoikis is a matrix detachment-induced apoptosis, also known as cell death, mechanistically prevents cells from escaping their native extracellular metastasize new organs. Deciphering the regulators mechanisms of anoikis cancer urgently needed treat HCC. Several natural synthetic products induce HCC vivo models. Here, we first briefly summarize current understanding molecular regulation relevant involved metastasis. Then discuss potential pharmacological induction treatment against Finally, key limitations this paradigm propose possible strategies overcome them. Cumulatively review suggests that can be used promising modality

Language: Английский

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Mapping the evolution and research landscape of ferroptosis-targeted nanomedicine: insights from a scientometric analysis

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 25, 2024

Notable progress has been made in "ferroptosis-based nano drug delivery systems (NDDSs)" over the past 11 years. Despite ongoing absence of a comprehensive scientometric overview and up-to-date scientific mapping research, especially regarding evolution, critical research pathways, current landscape, central investigative themes, future directions.

Language: Английский

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Broadening horizons: research on ferroptosis in lung cancer and its potential therapeutic targets

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 23, 2025

Ferroptosis is a novel form of cell death distinct from traditional mechanisms, characterized by the accumulation iron ions and production lipid peroxides. It not only affects survival tumor cells but also closely linked to changes in microenvironment. Lung cancer one leading malignancies worldwide terms incidence mortality, its complex biological mechanisms resistance make treatment challenging. Recent studies have shown that ferroptosis plays key role onset progression lung cancer, with intricate regulatory influencing development response therapy. As research into deepens, related molecular pathways, such as glutamate metabolism, antioxidant defense, been gradually revealed. However, clinical practice, ferroptosis-based therapeutic strategies for are still their early stages. Challenges remain, including incomplete understanding specific ferroptosis, insufficient on factors, limited insight interactions within Therefore, effective modulation enhance remains an urgent issue. This review summarizes analyzes factors interaction microenvironment, further explores potential targeting ferroptosis. By synthesizing latest research, this paper aims provide new perspectives directions treatment, goal advancing applications.

Language: Английский

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EGFR influences the resistance to targeted therapy in BRAF V600E melanomas by regulating the ferroptosis process

Archives of Dermatological Research, Journal Year: 2025, Volume and Issue: 317(1)

Published: March 1, 2025

To identify genes differentially expressed between resistant and sensitive BRAF V600E melanoma cell lines using bioinformatics tools applied to GEO data. We retrieved downloaded the target gene set (GSE45558) from database used R software filter (DEGs) resistant. The identified DEGs were subjected GO functional enrichment analysis (including biological processes, molecular functions, cellular components) Kyoto Encyclopedia of Genes Genomes (KEGG) pathway analysis, utilizing software. Protein-protein interaction networks for generated STRING online database. Top hub cross-referenced with related ferroptosis FerrDb linked in cells. From we top 100 lines, including 50 downregulated upregulated DEGs. Using Cytoscape, 10 genes: IL6, IL1B, CCL2, MMP2, TGFB2, EGFR, POSTN, SERPINE1, COL1A2, MITF. Cross-referencing database, found that IL6 EGFR are Validation through clinical samples vitro experiments confirmed high expression ferroptosis-related as a potential biomarker resistance targeted therapy BRAFV600E melanoma. Bioinformatics key therapy, demonstrating impact on

Language: Английский

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Ferroptosis: emerging roles in lung cancer and potential implications in biological compounds

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 9, 2024

Lung cancer has high metastasis and drug resistance. The prognosis of lung patients is poor the patients’ survival chances are easily neglected. Ferroptosis a programmed cell death proposed in 2012, which differs from apoptosis, necrosis autophagy. novel type regulated driven by iron-dependent lipid peroxidation subsequent plasma membrane ruptures. It broad prospects field tumor disease treatment. At present, multiple studies have shown that biological compounds can induce ferroptosis cells, exhibits significant anti-cancer effects, they advantages safety, minimal side less possibility to In this review, we summarize used for treatment focusing on its mechanism. addition, systematically review current research status combining nanotechnology with treatment, shed new light targeting pathways applying compounds-based therapies.

Language: Английский

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