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1.
Phytother Res ; 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39363549

RESUMEN

Mentha aquatica L., or water mint, is an important member of the Mentha genus, and has long been used in traditional medicine, mainly to treat respiratory diseases such as the common cold. Nevertheless, although over the years many studies have shown that it's potential grows beyond this use, a review that highlights M. aquatica L.'s true potential is still lacking. Thus, the main purpose of the present article is to provide a thorough and multidisciplinary critical review of M. aquatica L., including its phytochemical characterization, main bioactivities, and current marketed cosmetic products. Many compounds have been identified as part of M. aquatica L. composition, such as terpenes, phenolic acids, phenols, and terpenoids, which have been linked to a vast therapeutic potential, namely anti-inflammatory, antioxidant, antibacterial, antifungal, antiobesity, and hepatoprotection bioactivities, with additional anticancer potential for several types of tumors (breast, lung, and skin), and psycho and neuroactive potential in depression, or Alzheimer's or Parkinson's disease. Additionally, it has been proven to be suitable for cosmetic application since several cleansing, hydrating, protecting, and/or odor masking products containing it are already available, with the main functions attributed to M. aquatica including refreshing/cooling effects, calming/soothing/relaxing effects, and purifying effects, properties closely related to its anti-inflammatory and antioxidant bioactivities. Hence, M. aquatica is an extremely versatile plant, with its extracts and essential oils having great therapeutic and cosmetic potential. With many marketed cosmetic products, future studies should focus on this plant's medicinal aspects, so that 1 day it can be part of therapeutic regimens.

2.
Clin Chim Acta ; 565: 119983, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39368685

RESUMEN

Exosomal non-coding RNAs (ncRNAs) have become essential contributors to advancing and treating lung cancers (LCs). The development of liquid biopsies that utilize exosomal ncRNAs (exo-ncRNAs) offers an encouraging method for diagnosing, predicting, and treating LC. This thorough overview examines the dual function of exo-ncRNAs as both indicators for early diagnosis and avenues for LC treatment. Exosomes are tiny vesicles secreted by various cells, including cancerous cells, enabling connection between cells by delivering ncRNAs. These ncRNAs, which encompass circular RNAs, long ncRNAs, and microRNAs, participate in the modulation of gene expression and cellular functions. In LC, certain exo-ncRNAs are linked to tumour advancement, spread, and treatment resistance, positioning them as promising non-invasive indicators in liquid biopsies. Additionally, targeting these ncRNAs offers potential for innovative treatment approaches, whether by suppressing harmful ncRNAs or reinstating the activity of tumour-suppressing ones. This review emphasizes recent developments in the extraction and analysis of exo-ncRNAs, their practical applications in LC treatment, and the challenges and prospects for translating these discoveries into clinical usage. Through this detailed examination of the current state of the art, we aim to highlight the significant potential of exo-ncRNAs for LC diagnostics and treatments.

3.
EXCLI J ; 23: 991-1017, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39253534

RESUMEN

One of the main causes of death worldwide is lung cancer, which is largely caused by cigarette smoking. The crucial transcription factor NF-κB, which controls inflammatory responses and various cellular processes, is a constitutively present cytoplasmic protein strictly regulated by inhibitors like IκB proteins. Upon activation by external stimuli, it undergoes phosphorylation, translocates into the nucleus, and modulates the expression of specific genes. The incontrovertible association between pulmonary malignancy and tobacco consumption underscores and highlights a public health concern. Polycyclic aromatic hydrocarbons and nitrosamines, potent carcinogenic compounds present in the aerosol emitted from combusted tobacco, elicit profound deleterious effects upon inhalation, resulting in severe perturbation of pulmonary tissue integrity. The pathogenesis of smoking-induced lung cancer encompasses an intricate process wherein NF-κB activation plays a pivotal role, triggered by exposure to cigarette smoke through diverse signaling pathways, including those associated with oxidative stress and pro-inflammatory cytokines. Unraveling the participation of NF-κB in smoking-induced lung cancer provides pivotal insights into molecular processes, wherein intricate crosstalk between NF-κB and pathways such as MAPK and PI3K-Akt amplifies the inflammatory response, fostering an environment conducive to the formation of lung cancer. This study reviews the critical function of NF-κB in the complex molecular pathways linked to the initiation and advancement of lung carcinogenesis as well as potential treatment targets. See also the graphical abstract(Fig. 1).

4.
Med Oncol ; 41(11): 252, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39320608

RESUMEN

Breast cancer (BC) is a leading global concern for women, with 30% being HER2-positive cases linked to poorer outcomes. Targeted therapies like trastuzumab deruxtecan (T-DXd), trastuzumab, pertuzumab, and T-DM1 have revolutionized HER2-positive metastatic breast cancer (MBC) treatment. Although these therapies have improved MBC management and patient outcomes, resistance can develop, reducing effectiveness. Personalized strategies based on tumor characteristics offer hope for better responses and longer outcomes. This review outlines insights into MBC patients responding well to anti-HER2 treatments, even across multiple treatment regimen. Recent immunotherapy, locoregional therapy, and liquid biopsy breakthroughs are covered, suggesting ways to increase long-term responders. Personalized approaches have boosted HER2-positive MBC outcomes, and ongoing research is crucial to uncover new treatments and biomarkers, potentially elevating long-term response rates and prognoses. This may aid in providing new direction to breast cancer clinics.


Asunto(s)
Neoplasias de la Mama , Medicina de Precisión , Receptor ErbB-2 , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Femenino , Receptor ErbB-2/metabolismo , Medicina de Precisión/métodos , Metástasis de la Neoplasia , Antineoplásicos Inmunológicos/uso terapéutico , Terapia Molecular Dirigida/métodos , Biomarcadores de Tumor/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inmunoterapia/métodos
6.
Pathol Res Pract ; 263: 155629, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39348749

RESUMEN

Chronic obstructive pulmonary disease (COPD) is strongly linked to cigarette smoke, which contains toxins that induce oxidative stress and airway inflammation, ultimately leading to premature airway epithelial cell senescence and exacerbating COPD progression. Current treatments for COPD are symptomatic and hampered by limited efficacy and severe side effects. This highlights the need to search for an optimal therapeutic candidate to address the root causes of these conditions. This study investigates the possible potential of poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles encapsulating the plant-based bioactive compound 18-ß-glycyrrhetinic acid (18ßGA) as a strategy to intervene in cigarette smoke extract (CSE)-induced oxidative stress, inflammation, and senescence, in vitro. We prepared 18ßGA-PLGA nanoparticles, and assessed their effects on cell viability, reactive oxygen species (ROS) production, anti-senescence properties (expression of senescence-associated ß galactosidase and p21 mRNA), and expression of pro-inflammatory genes (CXCL-1, IL-6, TNF-α) and inflammation-related proteins (IL-8, IL-15, RANTES, MIF). The highest non-toxic concentration of 18ßGA-PLGA nanoparticles to healthy human broncho epithelial cell line BCiNS1.1 was identified as 5 µM. These nanoparticles effectively mitigated cigarette smoke-induced inflammation, reduced ROS production, protected against cellular aging, and counteracted the effects of CSE on the expression of the inflammation-related genes and proteins. This study underscores the potential of 18ßGA encapsulated in PLGA nanoparticles as a promising therapeutic approach to alleviate cigarette smoke-induced oxidative stress, inflammation, and senescence. Further research is needed to explore the translational potential of these findings in clinical and in vivo settings.

7.
MedComm (2020) ; 5(10): e745, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39329017

RESUMEN

Patient-derived xenografts (PDX) involve transplanting patient cells or tissues into immunodeficient mice, offering superior disease models compared with cell line xenografts and genetically engineered mice. In contrast to traditional cell-line xenografts and genetically engineered mice, PDX models harbor the molecular and biologic features from the original patient tumor and are generationally stable. This high fidelity makes PDX models particularly suitable for preclinical and coclinical drug testing, therefore better predicting therapeutic efficacy. Although PDX models are becoming more useful, the several factors influencing their reliability and predictive power are not well understood. Several existing studies have looked into the possibility that PDX models could be important in enhancing our knowledge with regard to tumor genetics, biomarker discovery, and personalized medicine; however, a number of problems still need to be addressed, such as the high cost and time-consuming processes involved, together with the variability in tumor take rates. This review addresses these gaps by detailing the methodologies to generate PDX models, their application in cancer research, and their advantages over other models. Further, it elaborates on how artificial intelligence and machine learning were incorporated into PDX studies to fast-track therapeutic evaluation. This review is an overview of the progress that has been done so far in using PDX models for cancer research and shows their potential to be further improved in improving our understanding of oncogenesis.

8.
Eur J Pharmacol ; 981: 176914, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39154820

RESUMEN

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous cancer that lacks all three molecular markers, Estrogen, Progesterone, and Human Epidermal Growth Factor Receptor 2 (HER2). This unique characteristic of TNBC makes it more resistant to hormonal therapy; hence, chemotherapy and surgery are preferred. Active targeting with nanoparticles is more effective in managing TNBC than a passive approach. The surface of TNBC cells overexpresses several cell-specific proteins, which can be explored for diagnostic and therapeutic purposes. Immunohistochemical analysis has revealed that TNBC cells overexpress αVß3 integrin, Intercellular Adhesion Molecule 1 (ICAM-1), Glucose Transporter 5 (GLUT5), Transmembrane Glycoprotein Mucin 1 (MUC-1), and Epidermal Growth Factor Receptor (EGFR). These surface proteins can be targeted using ligands, such as aptamers, antibodies, and sugar molecules. Targeting the surface proteins of TNBC with ligands helps harmonize treatment and improve patient compliance. In this review, we discuss the proteins expressed, which are limited to αVß3 integrin proteins, ICAM-1, GLUT-5, MUC1, and EGFR, on the surface of TNBC, the challenges associated with the preclinical setup of breast cancer for targeted nanoformulations, internalization techniques and their challenges, suggestions to overcome the limitations of successful translation of nanoparticles, and the possibility of ligand-conjugated nanoparticles targeting these surface receptors for a better therapeutic outcome.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Animales , Nanopartículas , Proteínas de la Membrana/metabolismo , Terapia Molecular Dirigida/métodos , Femenino , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología
9.
Pathol Res Pract ; 262: 155546, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39191194

RESUMEN

Colorectal cancer (CRC) is an abnormal proliferation of cells within the colon and rectum, leading to the formation of polyps and disruption of mucosal functions. The disease development is influenced by a combination of factors, including inflammation, exposure to environmental mutagens, genetic alterations, and impairment in signaling pathways. Traditional treatments such as surgery, radiation, and chemotherapy are often used but have limitations, including poor solubility and permeability, treatment resistance, side effects, and post-surgery issues. Novel Drug Delivery Systems (NDDS) have emerged as a superior alternative, offering enhanced drug solubility, precision in targeting cancer cells, and regulated drug release. Thereby addressing the shortcomings of conventional therapies and showing promise for more effective CRC management. The present review sheds light on the pathogenesis, signaling pathways, biomarkers, conventional treatments, need for NDDS, and application of NDDS against CRC. Additionally, clinical trials, ongoing clinical trials, marketed formulations, and patents on CRC are also covered in the present review.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Sistemas de Liberación de Medicamentos , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Antineoplásicos/uso terapéutico , Animales
11.
Curr Med Chem ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39162280

RESUMEN

Liquiritin (LIQ), a bioactive flavonoid from Glycyrrhiza species, has shown significant potential in cancer therapy. LIQ exhibits potent inhibitory effects on various cancer cell types, including breast, lung, liver, and colon cancers, while demonstrating low toxicity towards healthy cells. Its anticancer mechanisms include inducing cell cycle arrest, promoting apoptosis, and modulating inflammation-related pathways. Additionally, LIQ impedes angiogenesis and enhances the efficacy of conventional chemotherapies through sensitization and synergistic effects with other natural compounds and targeted therapies. These multifaceted actions highlight LIQ as a promising candidate for further development as an anticancer agent. This abstract provides an overview of LIQ's chemistry, biological effects, and underlying mechanisms.

12.
Pathol Res Pract ; 261: 155490, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39126977

RESUMEN

Pyroptosis is an inflammatory programed cell death process that plays a crucial role in cancer therapeutic, while Gasdermin-D is a critical effector protein for pyroptosis execution. This review discusses the intricate interactions between Gasdermin-D and some non-coding RNAs (lncRNA, miRNA, siRNA) and their potential application in the regulation of pyroptosis as an anticancer therapy. Correspondingly, these ncRNAs significantly implicate in Gasdermin-D expression and function regarding the pyroptosis pathway. Functioning as competing endogenous RNAs (ceRNAs), these ncRNAs might regulate Gasdermin-D at the molecular level, underlying fatal cell death caused by cancer and tumor propagation. Therefore, these interactions appeal to therapeutics, offering new avenues for cancer treatment. It address this research gap by discussing the possible roles of ncRNAs as mediators of gasdermin-D regulation. It suggest therapeutic strategies based on the current research findings to ensure the interchange between the ideal pyroptosis and cancer cell death.


Asunto(s)
Péptidos y Proteínas de Señalización Intracelular , Neoplasias , Proteínas de Unión a Fosfato , Piroptosis , ARN no Traducido , Piroptosis/fisiología , Humanos , Neoplasias/patología , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/terapia , Proteínas de Unión a Fosfato/metabolismo , Proteínas de Unión a Fosfato/genética , ARN no Traducido/genética , ARN no Traducido/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Animales , Regulación Neoplásica de la Expresión Génica , Gasderminas
13.
Int Immunopharmacol ; 141: 112913, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39137633

RESUMEN

Chronic respiratory diseases such as Chronic Obstructive Pulmonary Disease (COPD) and asthma have posed a significant healthcare and economic cost over a prolonged duration worldwide. At present, available treatments are limited to a range of preventive medicines, such as mono- or multiple-drug therapy, which necessitates daily use and are not considered as viable treatments to reverse the inflammatory processes of airway remodelling which is inclusive of the alteration of intra and extracellular matrix of the airway tract, death of epithelial cells, the increase in smooth muscle cell and the activation of fibroblasts. Hence, with the problem in mind a considerable body of study has been dedicated to comprehending the underlying factors that contribute to inflammation within the framework of these disorders. Hence, adequate literature that has unveiled the necessary cellular probing to reduce inflammation in the respiratory tract by improving the selectivity and precision of a novel treatment. However, through cellular probing cellular mechanisms such as the downregulation of various markers, interleukin 8, (IL-8), Interleukin 6 (IL-6), interleukin 1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) have been uncovered. Hence, to target such cellular probes implementation of phytoceuticals encapsulated in an advanced drug delivery system has shown potential to be a solution with in vitro and in vivo studies highlighting their anti-inflammatory and antioxidant effects. However, the high costs associated with advanced drug delivery systems and the limited literature focused exclusively on nanoparticles pose significant challenges. Additionally, the biochemical characteristics of phytoceuticals due to poor solubility, limited bioavailability, and difficulties in mass production makes it difficult to implement this product as a treatment for COPD and asthma. This study aims to examine the integration of many critical features in the context of their application for the treatment of chronic inflammation in respiratory disorders.


Asunto(s)
Sistemas de Liberación de Medicamentos , Humanos , Animales , Antiinflamatorios/uso terapéutico , Antiinflamatorios/administración & dosificación , Fitoquímicos/uso terapéutico , Fitoquímicos/administración & dosificación , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico
14.
Curr Drug Deliv ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956909

RESUMEN

BACKGROUND: The therapeutic effect of NS oil in mild to moderate psoriasis is limited owing to low play load of thymoquinone ( < 15 %w/w), irritation, dripping, low viscosity and thus, less contact time on the lesions. AIMS: This study aimed at developing and characterizing the ethanolic vesicular hydrogel system of Nigella sativa (NS) oil (NS EV hydrogel) for the enhancement of anti-psoriatic activity. OBJECTIVE: The objective of this study was to develop NS EV hydrogel and evaluate its anti-psoriatic activity. METHODS: The identification and quantification of TQ content in different NS seed extracts and marketed oil were measured by an HPTLC method using n-hexane and ethyl acetate as solvent systems. Preparation of ethanolic vesicles (EVs) was performed by solvent injection method, while its antipsoriatic activity was evaluated employing an Imiquad (IMQ)-induced plaque psoriasis animal model. RESULTS: A compact HPTLC band was obtained for TQ at an Rf value of 0.651. The calibration plot was linear in the range of 1-10 µg/spot, and the correlation coefficient of 0.990 was indicative of good linear dependence of peak area on concentration. From the different NS sources, the high TQ content was obtained in the marketed cold press oil, i.e., 1.45±0.08mg/ml. Out of various NS oilloaded EVs, the F6 formulation revealed the smallest particle size (278.1nm), with log-normal size distribution (0.459) and adequate entrapment efficiency. A non-uniform shape was observed in the transmission electron microscopy. The viscosity of F6 formulation hydrogel was 32.34 (Pa·s), which exhibited plastic behavior. In vivo, efficacy studies demonstrated decreased inflammation of the epidermis and dermis and a marked decrease in the levels of IL-17 by NS EV hydrogel compared to plain NS oil and standard drugs (Betamethasone and Dr. JRK Psorolin Oil). CONCLUSION: It may be concluded from the findings that NS-loaded EV gel was as good as betamethasone cream but more efficacious than the other treatments.

15.
Noncoding RNA Res ; 9(4): 1222-1234, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39036600

RESUMEN

Ferroptosis, a form of regulated cell death, has emerged as a crucial process in diverse pathophysiological states, encompassing cancer, neurodegenerative ailments, and ischemia-reperfusion injury. The glutathione (GSH)-dependent lipid peroxidation pathway, chiefly governed by glutathione peroxidase 4 (GPX4), assumes an essential part in driving ferroptosis. GPX4, as the principal orchestrator of ferroptosis, has garnered significant attention across cancer, cardiovascular, and neuroscience domains over the past decade. Noteworthy investigations have elucidated the indispensable functions of ferroptosis in numerous diseases, including tumorigenesis, wherein robust ferroptosis within cells can impede tumor advancement. Recent research has underscored the complex regulatory role of non-coding RNAs (ncRNAs) in regulating the GSH-GPX4 network, thus influencing cellular susceptibility to ferroptosis. This exhaustive review endeavors to probe into the multifaceted processes by which ncRNAs control the GSH-GPX4 network in ferroptosis. Specifically, we delve into the functions of miRNAs, lncRNAs, and circRNAs in regulating GPX4 expression and impacting cellular susceptibility to ferroptosis. Moreover, we discuss the clinical implications of dysregulated interactions between ncRNAs and GPX4 in several conditions, underscoring their capacity as viable targets for therapeutic intervention. Additionally, the review explores emerging strategies aimed at targeting ncRNAs to modulate the GSH-GPX4 pathway and manipulate ferroptosis for therapeutic advantage. A comprehensive understanding of these intricate regulatory networks furnishes insights into innovative therapeutic avenues for diseases associated with perturbed ferroptosis, thereby laying the groundwork for therapeutic interventions targeting ncRNAs in ferroptosis-related pathological conditions.

16.
Pathol Res Pract ; 260: 155387, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38870713

RESUMEN

Lung cancer (LC) is the leading cause of cancer-related mortality, and it is caused by many factors including cigarette smoking. Despite numerous treatment strategies for LC, its five-year survival is still poor (<20 %), attributable to treatment resistance and lack of early diagnosis and intervention. Importantly, LC incidence is higher in patients affected by chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disorder (COPD), and LC shares with other CRDs common pathophysiological features including chronic inflammation, oxidative stress, cellular senescence, and airway remodelling. Remodelling is a complex process resulting from the aberrant activation of tissue repair secondary to chronic inflammation, oxidative stress, and tissue damage observed in the airways of CRD patients, and it is characterized by irreversible airway structural and functional alterations, concomitantly with tissue fibrosis, epithelial-to-mesenchymal transition (EMT), excessive collagen deposition, and thickening of the basement membrane. Many processes involved in remodelling, particularly EMT, are also fundamental for LC pathogenesis, highlighting a potential connection between CRDs and LC. This provides rationale for the development of novel treatment strategies aimed at targeting components of the remodelling pathways. In this study, we tested the in vitro therapeutic activity of rat fecal microbiome extract (FME) on A549 human lung adenocarcinoma cells. We show that treatment with FME significantly downregulates the expression of six proteins whose function is at the forefront between airway remodelling and LC development: Snail, SPARC, MUC-1, Osteopontin, MMP-2, and HIF-1α. The results of this study, if confirmed by further investigations, provide proof-of-concept for a novel approach in the treatment of LC, focused on tackling the airway remodelling mechanisms underlying the increased susceptibility to develop LC observed in CRD patients.


Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias) , Regulación hacia Abajo , Neoplasias Pulmonares , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Animales , Ratas , Células A549 , Heces/microbiología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Microbiota/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos
17.
Pathol Res Pract ; 260: 155423, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38909404

RESUMEN

Curcumin, the principal curcuminoid of turmeric (Curcuma longa extract), is very well known for its multiple biological therapeutic activities, particularly its anti-inflammatory and antioxidant potential. However, due to its low water solubility, it exhibits poor bioavailability. In order to overcome this problem, in the current study, we have employed liposomal technology to encapsulate curcumin with the aim of enhancing its therapeutic efficacy. The curcumin-loaded liposomes (PlexoZome®) were tested on a cigarette smoke extract-induced Chronic Obstructive Pulmonary Disease (COPD) in vitro model using minimally immortalized human bronchial epithelial cells (BCiNS1.1). The anti-senescence and anti-inflammatory properties of PlexoZome® were explored. 5 µM PlexoZome® curcumin demonstrated anti-senescent activity by decrease in X-gal positive cells, and reduction in the expression of p16 and p21 in immunofluorescence staining. Moreover, PlexoZome® curcumin also demonstrated a reduction in proteins related to senescence (osteopontin, FGF basic and uPAR) and inflammation (GM-CSF, EGF and ST2). Overall, the results clearly demonstrate the therapeutic potential of curcumin encapsulated liposomes in managing CSE induced COPD, providing a new direction to respiratory clinics.


Asunto(s)
Senescencia Celular , Curcumina , Células Epiteliales , Inflamación , Liposomas , Curcumina/farmacología , Humanos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Senescencia Celular/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/patología , Inflamación/metabolismo , Bronquios/patología , Bronquios/efectos de los fármacos , Bronquios/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Humo/efectos adversos , Antiinflamatorios/farmacología , Línea Celular
18.
Life Sci ; 352: 122859, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38925223

RESUMEN

Lung cancer is among leading causes of death worldwide. The five-year survival rate of this disease is extremely low (17.8 %), mainly due to difficult early diagnosis and to the limited efficacy of currently available chemotherapeutics. This underlines the necessity to develop innovative therapies for lung cancer. In this context, drug repurposing represents a viable approach, as it reduces the turnaround time of drug development removing costs associated to safety testing of new molecular entities. Ribavirin, an antiviral molecule used to treat hepatitis C virus infections, is particularly promising as repurposed drug for cancer treatment, having shown therapeutic activity against glioblastoma, acute myeloid leukemia, and nasopharyngeal carcinoma. In the present study, we thoroughly investigated the in vitro anticancer activity of ribavirin against A549 human lung adenocarcinoma cells. From a functional standpoint, ribavirin significantly inhibits cancer hallmarks such as cell proliferation, migration, and colony formation. Mechanistically, ribavirin downregulates the expression of numerous proteins and genes regulating cell migration, proliferation, apoptosis, and cancer angiogenesis. The anticancer potential of ribavirin was further investigated in silico through gene ontology pathway enrichment and protein-protein interaction networks, identifying five putative molecular interactors of ribavirin (Erb-B2 Receptor Tyrosine Kinase 4 (Erb-B4); KRAS; Intercellular Adhesion Molecule 1 (ICAM-1); amphiregulin (AREG); and neuregulin-1 (NRG1)). These interactions were characterized via molecular docking and molecular dynamic simulations. The results of this study highlight the potential of ribavirin as a repurposed chemotherapy against lung cancer, warranting further studies to ascertain the in vivo anticancer activity of this molecule.


Asunto(s)
Antineoplásicos , Proliferación Celular , Reposicionamiento de Medicamentos , Neoplasias Pulmonares , Ribavirina , Humanos , Reposicionamiento de Medicamentos/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Ribavirina/farmacología , Células A549 , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Movimiento Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Simulación del Acoplamiento Molecular , Antivirales/farmacología , Biología Computacional/métodos , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo
19.
EXCLI J ; 23: 570-599, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887390

RESUMEN

Cancer poses intricate challenges to treatment due to its complexity and diversity. Ferroptosis and circular RNAs (circRNAs) are emerging as innovative therapeutic avenues amid the evolving landscape of cancer therapy. Extensive investigations into circRNAs reveal their diverse roles, ranging from molecular regulators to pivotal influencers of ferroptosis in cancer cell lines. The results underscore the significance of circRNAs in modulating molecular pathways that impact crucial aspects of cancer development, including cell survival, proliferation, and metastasis. A detailed analysis delineates these pathways, shedding light on the molecular mechanisms through which circRNAs influence ferroptosis. Building upon recent experimental findings, the study evaluates the therapeutic potential of targeting circRNAs to induce ferroptosis. By identifying specific circRNAs associated with the etiology of cancer, this analysis paves the way for the development of targeted therapeutics that exploit vulnerabilities in cancer cells. This review consolidates the existing understanding of ferroptosis and circRNAs, emphasizing their role in cancer therapy and providing impetus for ongoing research in this dynamic field. See also the graphical abstract(Fig. 1).

20.
Drug Deliv Transl Res ; 14(9): 2325-2344, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38758498

RESUMEN

Skin cancer remains one of the most prominent types of cancer. Melanoma and non-melanoma skin cancer are commonly found together, with melanoma being the more deadly type. Skin cancer can be effectively treated with chemotherapy, which mostly uses small molecular medicines, phytoceuticals, and biomacromolecules. Topical delivery of these therapeutics is a non-invasive way that might be useful in effectively managing skin cancer. Different skin barriers, however, presented a major obstacle to topical cargo administration. Transferosomes have demonstrated significant potential in topical delivery by improving cargo penetration through the circumvention of diverse skin barriers. Additionally, the transferosome-based gel can prolong the residence of drug on the skin, lowering the frequency of doses and their associated side effects. However, the choice of appropriate transferosome compositions, such as phospholipids and edge activators, and fabrication technique are crucial for achieving improved entrapment efficiency, penetration, and regulated particle size. The present review discusses skin cancer overview, current treatment strategies for skin cancer and their drawbacks. Topical drug delivery against skin cancer is also covered, along with the difficulties associated with it and the importance of transferosomes in avoiding these difficulties. Additionally, a summary of transferosome compositions and fabrication methods is provided. Furthermore, topical delivery of small molecular drugs, phytoceuticals, and biomacromolecules using transferosomes and transferosomes-based gel in treating skin cancer is discussed. Thus, transferosomes can be a significant option in the topical delivery of drugs to manage skin cancer efficiently.


Asunto(s)
Antineoplásicos , Liposomas , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Animales , Administración Cutánea , Sistemas de Liberación de Medicamentos , Absorción Cutánea
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