Design and Computational Analysis of an MMP9 Inhibitor in Hypoxia-Induced Glioblastoma Multiforme

ACS Omega, Год журнала: 2023, Номер 8(11), С. 10565 - 10590

Опубликована: Март 13, 2023

The main therapeutic difficulties in treating hypoxia-induced glioblastoma multiforme (GBM) are toxicity of current treatments and the resistance brought on by microenvironment. More effective alternatives urgently needed to reduce tumor lethality. Hence, we screened plant-based natural product panels intending identify novel drugs without elevating drug resistance. We explored GEO for hypoxia GBM model compared hypoxic genes non-neoplastic brain cells. A total 2429 differentially expressed exclusively were identified. functional enrichment analysis demonstrated associated with GBM, further PPI network was constructed, biological pathways them explored. Seven webtools, including GEPIA2.0, TIMER2.0, TCGA-GBM, GlioVis, used validate 32 hub discovered using Cytoscape tool patient samples. Four GBM-specific genes, LYN, MMP9, PSMB9, TIMP1, connected microenvironment TIMER analysis. 11 promising hits positive drug-likeness nontoxic characteristics successfully crossed blood-brain barrier ADMET analyses. Top-ranking have stable intermolecular interactions MMP9 protein according molecular docking, MD simulation, MM-PBSA, PCA, DCCM Herein, reported flavonoids, 7,4'-dihydroxyflavan, (3R)-3-(4-hydroxybenzyl)-6-hydroxy-8-methoxy-3,4-dihydro-2H-1-benzopyran, 4'-hydroxy-7-methoxyflavan, inhibit a gene signature that could serve as predictor various clinical applications, diagnosis, prognosis, targeted therapy.

Язык: Английский

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Systemic Effects Reflected in Specific Biomarker Patterns Are Instrumental for the Paradigm Change in Prostate Cancer Management: A Strategic Paper

Cancers, Год журнала: 2022, Номер 14(3), С. 675 - 675

Опубликована: Янв. 28, 2022

Prostate cancer (PCa) is reported as the most common malignancy and second leading cause of death in America. In Europe, PCa considered type tumour 28 European countries. The costs treating are currently increasing more rapidly than those any other cancer. Corresponding economic burden enormous, due to an overtreatment slowly developing disease on one hand underestimation/therapy resistance particularly aggressive subtypes hand. incidence metastatic that characteristic for young adults. a systemic multi-factorial resulting from imbalanced interplay between risks protective factors. Sub-optimal behavioural patterns, abnormal stress reactions, antioxidant defence, ischemia inflammation, mitochondriopathies, aberrant metabolic pathways, gene methylation damage DNA, amongst others, synergistically involved pathomechanisms development progression. To this end, PCa-relevant effects reflected liquid biopsies such blood patterns which instrumental predictive diagnostics, targeted prevention personalisation medical services (PPPM/3P medicine) new paradigm overall management. This strategic review article highlights prostate progression, demonstrates evident challenges management provides expert recommendations framework 3P medicine.

Язык: Английский

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Decoding the Role of MDM2 as a Potential Ubiquitin E3 Ligase and Identifying the Therapeutic Efficiency of Alkaloids against MDM2 in Combating Glioblastoma

ACS Omega, Год журнала: 2023, Номер 8(5), С. 5072 - 5087

Опубликована: Янв. 26, 2023

Glioblastomas (GBMs) represent the most aggressive form of brain tumor arising from malignant transformation astrocytes. Despite various advancements, treatment options remain limited to chemotherapy and radiotherapy followed by surgery giving an overall survival 14–15 months. These therapies are somewhere restricted in a better cure. There is need for new therapeutics that could potentially target GBM based on molecular pathways pathology. Here, ubiquitin E3 ligases can be used as targets they bind wide array substrates therefore attractive inhibitors. Through this study, we have tried sort their expression, which these associated, mutational frequencies, then screen potent inhibitors against favorable ligase very few studies available concerning inhibition GBM. Our study found MDM2 ideal further compounds under alkaloid class. Molecular Docking MD simulations combined with ADMET properties BBB scores revealed only evodiamine sanguinarine were effective inhibiting MDM2. We also give proposed mechanism how mediate p53 signaling Therefore, scaffolds predicted computational approach help designing promising therapeutic agents targeting glioblastoma.

Язык: Английский

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The effect of Azo-dyes on glioblastoma cells in vitro

Saudi Journal of Biological Sciences, Год журнала: 2023, Номер 30(3), С. 103599 - 103599

Опубликована: Фев. 14, 2023

Despite the multidisciplinary standard treatment of glioblastoma (GB) consisting maximal surgical resection, followed by radiotherapy (RT) plus concomitant chemotherapy with temozolomide (TMZ), majority patients experience tumor progression and almost universal mortality. In recent years, efforts have been made to create new agents for GB treatment, which azo-dyes proved be potential candidates, showing antiproliferative effects inducing apoptosis inhibiting different signaling pathways. this study we evaluated effect six TMZ on a low passage human cell line using MTT assay. We found that all compounds properties cells. At equimolar concentrations induced more cytotoxic than TMZ. Methyl Orange required lowest IC50 3 days (26.4684 μM), whilst 7 two azo dyes highest potency: = 13.8808 μM Sudan I 12.4829 μM. The was determined under both experimental situations. Conclusions: Our research represents novelty, offering unique valuable data regarding azo-dye cyototoxic in high grade brain tumors. This may focus attention represent an insufficient exploited source cancer treatment.

Язык: Английский

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The Prognosis of Cancer Depends on the Interplay of Autophagy, Apoptosis, and Anoikis within the Tumor Microenvironment

Cell Biochemistry and Biophysics, Год журнала: 2023, Номер 81(4), С. 621 - 658

Опубликована: Окт. 3, 2023

Язык: Английский

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A review of natural products and small‐molecule therapeutics acting on central nervous system malignancies: Approaches for drug development, targeting pathways, clinical trials, and challenges

Drug Development Research, Год журнала: 2024, Номер 85(3)

Опубликована: Апрель 29, 2024

In 2021, the World Health Organization released fifth edition of central nervous system (CNS) tumor classification. This classification uses histopathology and molecular pathogenesis to group tumors into more biologically molecularly defined entities. The prognosis brain cancer, particularly malignant tumors, has remained poor worldwide, approximately 308,102 new cases other CNS were diagnosed in year 2020, with an estimated 251,329 deaths. cost time-consuming nature studies find anticancer agents makes it necessary have well-designed studies. present study, pathways that can be targeted for drug development are discussed detail. Some important cellular origins, signaling, involved efficacy bioactive molecules against tumorigenesis or progression, as well common approaches treatment different types reviewed. Moreover, study tools, including cell lines, vitro, vivo, clinical trial challenges, discussed. addition, this article, natural products one most sources finding chemotherapeutics reviewed over 700 reported cancer cells gathered classified according their structure. Based on trials been registered, very few these semi-synthetic derivatives studied humans. review help researchers understand mechanisms design goal-oriented malignancies.

Язык: Английский

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Protective Role of an Extract Waste Product From <em>Citrus bergamia</em> in an In Vitro Model of Neurodegeneration

Опубликована: Май 11, 2023

A balanced diet model, rich in fruits and vegetables ensuring the intake of natural products, has been shown to reduce or prevent occurrence many chronic diseases. However, choice consume large quantities leads an increase amount waste, which can cause alteration environmental sustainability. To date, concept &quot;by-product&quot; evolved, understood as a waste product, from it is still possible obtain useful compounds. Therefore, by-products agricultural sector, are source bioactive compounds, capable possess second life, decreasing disposal costs pollution. promising well-known citrus Mediterranean bergamot (Citrus bergamia, Risso et Poiteau). The composition known presence phenolic compounds essential oils justified countless beneficial properties found, including anti-inflammatory, antioxidant, anti-cholesterolemic protective activity for immune system, heart failure coronary industrial processing formation juice oil. solid residues, referred &quot;pastazzo&quot;, normally used feed livestock pectin production. fiber (BF) be obtained pastazzo could exert interesting effect thanks its content polyphenols. purpose this work was test effects BF on vitro model neurotoxicity induced by treatment with amyloid beta protein. In particular, experimental included both neurons oligodendrocytes order measure involvement glia compare one. results showed BF, although were more sensitive fragile than neurons. Further experiments necessary if trend confirmed, residues AD, and, at same time, help avoid accumulation products.

Язык: Английский

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A Novel Strategy for Glioblastoma Treatment by Natural Bioactive Molecules Showed a Highly Effective Anti-Cancer Potential

Nutrients, Год журнала: 2024, Номер 16(15), С. 2389 - 2389

Опубликована: Июль 23, 2024

Glioblastoma (GBM) is a severe form of brain tumor that has high fatality rate. It grows aggressively and most the time results in resistance to traditional treatments like chemo- radiotherapy surgery

Язык: Английский

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Siderol Inhibits Proliferation of Glioblastoma Cells and Acts Synergistically with Temozolomide

Biomedicines, Год журнала: 2022, Номер 10(12), С. 3216 - 3216

Опубликована: Дек. 12, 2022

Glioblastoma (GBM) is the most aggressive primary central nervous system (CNS) tumor in adults with dismal prognosis. Currently, therapeutic interventions include gross total resection, when possible, followed by radiotherapy and chemotherapy. However, despite treatment, usually recurs within 7-9 months. The presence of glioma cells stem-like properties tumor's heterogeneity have been identified as important factors driving recurrence. Recently, research efforts focused on use natural substances treatment for GBM. Siderol an ent-kaurane diterpenoid, isolated from genus Sideritis. Sideritis extracts already investigated their anti-inflammatory, antioxidant, anticancer effects. In this study, we antitumoral effects siderol GBM T98 U87 cell lines, well combined temozolomide (TMZ). Cell viability was evaluated 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay trypan blue exclusion assay. Different concentrations were used order to calculate IC50 values at 72 h after treatment. Flow cytometry DNA cycle analysis twice h. Furthermore, effect cell's migratory ability tested using wound healing proliferation, TMZ, also combination analyzed CompuSyn software. Treatment significantly reduced lines a dose-dependent manner calculated, 18 μM 13 μM, respectively. Moreover, induced G0/G1 arrest inhibited migration both lines. addition, TMZ seem synergistic action majority cells. conclusion, may represent innovative strategy GBM, further studies are needed siderol's efficacy mode action.

Язык: Английский

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Recent insights into nanoformulation delivery systems of flavonoids against glioblastoma

Journal of Drug Delivery Science and Technology, Год журнала: 2023, Номер 91, С. 105271 - 105271

Опубликована: Дек. 19, 2023

Язык: Английский

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