Drug Repurposing: The Mechanisms and Signaling Pathways of Anti-Cancer Effects of Anesthetics

Biomedicines, Год журнала: 2022, Номер 10(7), С. 1589 - 1589

Опубликована: Июль 4, 2022

Cancer is one of the leading causes death worldwide. There are only limited treatment strategies that can be applied to treat cancer, including surgical resection, chemotherapy, and radiotherapy, but these have effectiveness. Developing a new drug for cancer therapy protracted, costly, inefficient. Recently, repurposing has become rising research field provide meaning an old drug. By searching database ReDO_DB, brief list anesthetic/sedative drugs, such as haloperidol, ketamine, lidocaine, midazolam, propofol, valproic acid, shown possess anti-cancer properties. Therefore, in current review, we will general overview mechanisms drugs explore potential underlying signaling pathways clinical application individually or combination with other agents.

Язык: Английский

---

Differential Impact of Valproic Acid on SLC5A8, SLC12A2, SLC12A5, CDH1, and CDH2 Expression in Adult Glioblastoma Cells

Biomedicines, Год журнала: 2024, Номер 12(7), С. 1416 - 1416

Опубликована: Июнь 25, 2024

Valproic acid (VPA) has anticancer, anti-inflammatory, and epigenetic effects. The study aimed to determine the expression of carcinogenesis-related

Язык: Английский

---

Histone Deacetylase Inhibitors as Cognitive Enhancers and Modifiers of Mood and Behavior

Current Drug Targets, Год журнала: 2022, Номер 24(9), С. 728 - 750

Опубликована: Дек. 7, 2022

Epigenetic regulation of gene signalling is one the fundamental molecular mechanisms for generation and maintenance cellular memory. Histone acetylation a common epigenetic mechanism associated with increased transcription in central nervous system (CNS). Stimulation by histone important development CNS-based long-term target cognitive enhancement via application deacetylase (HDAC) inhibitors. The promising potential HDAC inhibitors has been observed treatment several neurodevelopmental neurodegenerative diseases.This study assessed current state inhibition as an approach to diseases. Our analysis provides insights into action inhibitors, priming, describes therapeutic success complications after unsupervised use inhibitors.Several chromatin-modifying enzymes play key roles processes. importance signaling brain highlighted this review. Recent advancements field epigenetics are supported successful various demonstrating effective mood-associated disorders. review discusses mood therapies.

Язык: Английский

---

Cross-reactivity between histone demethylase inhibitor valproic acid and DNA methylation in glioblastoma cell lines

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Ноя. 16, 2022

Currently, valproic acid (VPA) is known as an inhibitor of histone deacetylase (epigenetic drug) and used for the clinical treatment epileptic events in course glioblastoma multiforme (GBM). Which improves outcome those patients. We analyzed level 5-methylcytosine, a DNA epigenetic modulator, 8-oxodeoxyguanosine, cellular oxidative damage marker, affected with VPA administration, alone combination temozolomide (TMZ), glioma (T98G, U118, U138), other cancer (HeLa), normal (HaCaT) cell lines. observed dose-dependent changes total methylation neoplastic lines lack such effect line. at high concentrations (250-500 μM) induced hypermethylation short time frame. However, exposition GBM cells to TMZ resulted hypomethylation. At same time, we increase genomic 8-oxo-dG, which hydroxyl radical reaction product guanosine residue suggests red-ox imbalance DNA. Our data show that HDAC does not induce only acetylation, but also state modification. It shows cross-reactivity between chromatin remodeling due acetylation methylation. Finally, cytosine oxidation under suggest new mechanism drug action.

Язык: Английский

---

Ligand-Gated Ion Channels: Prognostic and Therapeutic Implications for Gliomas

Journal of Personalized Medicine, Год журнала: 2023, Номер 13(5), С. 853 - 853

Опубликована: Май 19, 2023

Gliomas are common primary brain malignancies that remain difficult to treat due their overall aggressiveness and heterogeneity. Although a variety of therapeutic strategies have been employed for the treatment gliomas, there is increasing evidence suggests ligand-gated ion channels (LGICs) can serve as valuable biomarker diagnostic tool in pathogenesis gliomas. Various LGICs, including P2X, SYT16, PANX2, potential become altered glioma, which disrupt homeostatic activity neurons, microglia, astrocytes, further exacerbating symptoms progression glioma. Consequently, purinoceptors, glutamate-gated receptors, Cys-loop targeted clinical trials benefit diagnosis In this review, we discuss role LGICs genetic factors effect LGIC on biological functioning neuronal cells. Additionally, current emerging investigations regarding use target

Язык: Английский

---

Drug Repurposing in Pediatric Brain Tumors: Posterior Fossa Ependymoma and Diffuse Midline Glioma under the Looking Glass

Frontiers in Bioscience-Landmark, Год журнала: 2023, Номер 28(4)

Опубликована: Апрель 24, 2023

Tumors of the Central Nervous System (CNS) represent leading cause cancer-related deaths in children. Current treatment options are not curative for most malignant histologies, and intense preclinical clinical research is needed to develop more effective therapeutic interventions against these tumors, which meet FDA definition orphan diseases. Increased attention being paid repositioning already-approved drugs new anticancer indications as a fast-tracking strategy identifying therapies. Two pediatric CNS posterior fossa ependymoma (EPN-PF) type A diffuse midline glioma (DMG) H3K27-altered, share loss H3K27 trimethylation common epigenetic hallmark display early onset poor prognosis. These features suggest potentially druggable vulnerability. Successful tumors raises several challenges due location chemoresistance, drug blood-brain barrier penetration, likelihood adverse side effects. Recently, increasing evidence demonstrates interactions between tumor cell subpopulations supportive microenvironments (TMEs) including nerve, metabolic, inflammatory TMEs. findings use drugs, and/or multi-drug combinations, that attack both cells TME simultaneously. In this work, we present an overview existing concerning preclinically validated noncancer with antineoplastic activity. belong four pharmacotherapeutic classes: antiparasitic, neuroactive, anti-inflammatory. Preclinical undergoing trials patients brain special emphasis on EPN-PF DMG, summarized critically discussed.

Язык: Английский

---

Valproic acid regulates the miR-155/Jarid2 axis by affecting miR-155 promoter methylation in glioma

Acta Biochimica et Biophysica Sinica, Год журнала: 2023, Номер unknown

Опубликована: Ноя. 8, 2023

The most frequent primary brain tumor in adults is glioma, yet no effective curative treatments are currently available. Our previous study demonstrated the enhancing effects of JARID2 on glioma sensitivity to TMZ treatment. In this study, miR-155 predicted target JARID2. overexpressed clinical specimens and cell lines. overexpression cells enhances viability represses apoptosis. Through targeting, inhibits expression. inhibition apoptosis, whereas

Язык: Английский

---

From HDAC to Voltage-Gated Ion Channels: What’s Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer

Cancers, Год журнала: 2022, Номер 14(18), С. 4401 - 4401

Опубликована: Сен. 10, 2022

Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in last decades and deriving developed treatments, which significantly improved patients' outcome, occurrence resistance to therapies remains cause relapse mortality. Thus, efforts identifying new markers be exploited as cancer therapy are needed. This review will first give glance on diagnostic therapeutic significance histone deacetylase (HDAC) voltage gated ion channels (VGICs) cancer. Nevertheless, HDAC VGICs have also been reported through antiepileptic drugs (AEDs) seem exert their anticancer activity. should claimed great advantage. Indeed, due slowness drug approval procedures, attempt turn off-label use already approved medicines would highly preferable. Therefore, an updated accurate overview both preclinical clinical data commonly prescribed AEDs (mainly valproic acid, lamotrigine, carbamazepine, phenytoin gabapentin) breast, prostate, brain other cancers follow. Finally, at emerging administer by means opportunely designed delivery systems (DDSs), so limit toxicity improve bioavailability, given.

Язык: Английский

---

Machine Learning-Based Analysis of Glioma Grades Reveals Co-Enrichment

Cancers, Год журнала: 2022, Номер 14(4), С. 1014 - 1014

Опубликована: Фев. 17, 2022

Gliomas develop and grow in the brain central nervous system. Examining glioma grading processes is valuable for improving therapeutic challenges. One of most extensive repositories storing transcriptomics data gliomas The Cancer Genome Atlas (TCGA). However, such big cohorts should be processed with caution evaluated thoroughly as they can contain batch other effects. Furthermore, biological mechanisms cancer interactions among biomarkers. Thus, we applied an interpretable machine learning approach to discover relationships. This type transparent provides not only good predictability, but also reveals co-predictive features. In this study, corrected strong confounded effect TCGA data. We further used datasets perform comprehensive analysis on single-sample gene set enrichment scores using collections from Molecular Signature Database. rule-based classifiers, displayed networks co-enrichment related grades. Moreover, validated our results external cohorts. believe that utilizing may improve application validation any future studies. Finally, survival provided detailed explanations progression consequently, it support targeted treatment.

Язык: Английский

---

WP1234—A Novel Anticancer Agent with Bifunctional Activity in a Glioblastoma Model

Biomedicines, Год журнала: 2022, Номер 10(11), С. 2799 - 2799

Опубликована: Ноя. 3, 2022

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with a poor prognosis. Despite significant progress drug development, blood-brain barrier (BBB) continues to limit use of novel chemotherapeutics. Thus, our attention has been focused on design, synthesis, and testing small-molecule anticancer agents that are able penetrate BBB. One such compound D-glucose analog, 2-deoxy-D-glucose (2-DG), which inhibits glycolysis induces GBM cell death. 2-DG already tested clinical trials but was not approved as drug, part due inadequate pharmacokinetics. To improve pharmacokinetic properties 2-DG, series derivatives synthesized. Herein, we report biological effects WP1234, 2-ethylbutyric acid 3,6-diester can potentially release 2-ethylbutyrate inside cells when metabolized. Using biochemical assays examining viability, proliferation, protein apoptosis induction, assessed cytotoxic potential WP1234. WP1234 significantly reduced viability dose- time-dependent manner. The lactate ATP synthesis confirmed inhibition elicited by released 2-DG. Furthermore, an evaluation histone deacetylases (HDAC) activity revealed action resulted HDAC inhibition. Overall, these results demonstrated bifunctional molecule promising potential. Further experiments animal models toxicology studies needed evaluate efficacy safety this new derivative.

Язык: Английский

---