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1.
Macromolecules ; 57(10): 4906-4917, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38827961

RESUMO

The chain architecture and topology of macromolecules impact their physical properties and final performance, including their crystallization process. In this work, comb polymers constituted by poly(ethylene glycol), PEG, side chains, and a dithiol-yne-based ring polymer backbone have been studied, focusing on the micro- and nanostructures of the system, thermal behavior, and crystallization kinetics. The designed comb system allows us to investigate the role of a ring backbone, the impact of varying the distance between two neighboring side chains, and the effect of the molecular weight of the side chain. The results reflect that the governing factor in the crystalline properties is the molar mass of the side chains and that the tethering of PEG chains to the ring backbone brings important constraints to the crystallization process, reducing the crystallinity degree and slowing down the crystallization kinetics in comparison to analogue PEG homopolymers. We demonstrate that the effect of spatial hindrance in the comb-like PEG polymers drives the morphology toward highly ordered, self-assembled, semicrystalline superstructures with either extended interdigitated chain crystals or novel (for comb polymers) interdigitated folded chain lamellar crystals. These structures depend on PEG molecular weight, the distance between neighboring tethered PEG chains, and the crystallization conditions (nonisothermal versus isothermal). This work sheds light on the role of chain architecture and topology in the structure of comb-like semicrystalline polymers.

2.
ACS Appl Bio Mater ; 7(4): 2036-2053, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38525971

RESUMO

Cancer is one of the major causes of death worldwide, even the second foremost cause related to non-communicable diseases. Cancer cells typically possess several cellular and biological processes including, persistence, propagation, differentiation, cellular death, and expression of cellular-type specific functions. The molecular picture of carcinogenesis and progression is unwinding, and it appears to be a tangled combination of processes occurring within and between cancer cells and their surrounding tissue matrix. Polyphenols are plant secondary metabolites abundant in fruits, vegetables, cereals, and other natural plant sources. Natural polyphenols have implicated potential anticancer activity by various mechanisms involved in their antitumor action, including modulation of signaling pathways majorly related to cellular proliferation, differentiation, relocation, angiogenesis, metastatic processes, and cell death. The applications of polyphenols have been limited due to the hydrophobic nature and lower oral bioavailability that could be possibly overcome through encapsulating them into nanocarrier-mediated delivery systems, leading to improved anticancer activity. Nanoemulsions (NEs) possess diverse feasible properties, including greater surface area, modifiable surficial charge, higher half-life, site-specific targeting, and formulation imaging capability necessary to create a practical therapeutic impact, and have drawn increased attention in cancer therapy research. This review has summarized and discussed the basic concepts, classification, delivery approaches, and anticancer mechanism of various polyphenols and polyphenols-encapsulated nanoemulsions with improved cancer therapy.


Assuntos
Neoplasias , Polifenóis , Humanos , Polifenóis/farmacologia , Polifenóis/química , Neoplasias/metabolismo , Antioxidantes/química , Transdução de Sinais
3.
Appl Biochem Biotechnol ; 196(2): 1008-1043, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37314636

RESUMO

Over the last few decades, the application of nanoparticles (NPs) gained immense attention towards environmental and biomedical applications. NPs are ultra-small particles having size ranges from 1 to 100 nm. NPs loaded with therapeutic or imaging compounds have proved a versatile approach towards healthcare improvements. Among various inorganic NPs, zinc ferrite (ZnFe2O4) NPs are considered as non-toxic and having an improved drug delivery characteristics . Several studies have reported broader applications of ZnFe2O4 NPs for treating carcinoma and various infectious diseases. Additionally, these NPs are beneficial for reducing organic and inorganic environmental pollutants. This review discusses about various methods to fabricate ZnFe2O4 NPs and their physicochemical properties. Further, their biomedical and environmental applications have also been explored comprehensively.


Assuntos
Nanopartículas , Zinco , Nanopartículas/química , Compostos Férricos/química , Sistemas de Liberação de Medicamentos
4.
ACS Pharmacol Transl Sci ; 6(12): 1801-1816, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38093838

RESUMO

Hepatocellular carcinoma (HCC) remains one of the predominant causes of cancer-related mortality across the globe. It is attributed to obesity, excessive alcohol consumption, smoking, and infection by the hepatitis virus. Early diagnosis of HCC is essential, and local treatments such as surgical excision and percutaneous ablation are effective. Palliative systemic therapy, primarily with the tyrosine kinase inhibitor Sorafenib, is used in advanced cases. However, the prognosis for advanced HCC remains poor. This Review additionally describes the pathophysiological mechanisms of HCC, which include aberrant molecular signaling, genomic instability, persistent inflammation, and the paradoxical position of the immune system in promoting and suppressing HCC. The paper concludes by discussing the growing body of research on the relationship between mitochondria and HCC, suggesting that mitochondrial dysfunction may contribute to the progression of HCC. This Review focuses on immunological interactions between different mechanisms of HCC progression, including obesity, viral infection, and alcohol consumption.

5.
Mol Pharm ; 20(8): 3698-3740, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37486263

RESUMO

Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Several recent findings revealed cellular and molecular pathways that promote the development and initiation of malignancy when viruses cause an infection. Even, antiviral treatment has become an approach to eliminate the viral infections and prevent the activation of oncogenesis. Therefore, for a better understanding, the molecular pathogenesis of various oncogenic viruses like, hepatitis virus, human immunodeficiency viral (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV), could be explored, especially, to expand many potent antivirals that may escalate the apoptosis of infected malignant cells while sparing normal and healthy ones. Moreover, contemporary therapies, such as engineered antibodies antiviral agents targeting signaling pathways and cell biomarkers, could inhibit viral oncogenesis. This review elaborates the recent advancements in both natural and synthetic antivirals to control viral oncogenesis. The study also highlights the challenges and future perspectives of using antivirals in viral oncogenesis.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias , Humanos , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Herpesvirus Humano 4 , Carcinogênese , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Neoplasias/patologia , Antivirais/farmacologia , Antivirais/uso terapêutico
6.
ACS Omega ; 8(16): 14290-14320, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37125102

RESUMO

Cancer is ranked as the second leading cause of death globally. Traditional cancer therapies including chemotherapy are flawed, with off-target and on-target toxicities on the normal cells, requiring newer strategies to improve cell selective targeting. The application of nanomaterial has been extensively studied and explored as chemical biology tools in cancer theranostics. It shows greater applications toward stability, biocompatibility, and increased cell permeability, resulting in precise targeting, and mitigating the shortcomings of traditional cancer therapies. The nanoplatform offers an exciting opportunity to gain targeting strategies and multifunctionality. The advent of nanotechnology, in particular the development of smart nanomaterials, has transformed cancer diagnosis and treatment. The large surface area of nanoparticles is enough to encapsulate many molecules and the ability to functionalize with various biosubstrates such as DNA, RNA, aptamers, and antibodies, which helps in theranostic action. Comparatively, biologically derived nanomaterials perceive advantages over the nanomaterials produced by conventional methods in terms of economy, ease of production, and reduced toxicity. The present review summarizes various techniques in cancer theranostics and emphasizes the applications of smart nanomaterials (such as organic nanoparticles (NPs), inorganic NPs, and carbon-based NPs). We also critically discussed the advantages and challenges impeding their translation in cancer treatment and diagnostic applications. This review concludes that the use of smart nanomaterials could significantly improve cancer theranostics and will facilitate new dimensions for tumor detection and therapy.

7.
Cell Oncol (Dordr) ; 46(4): 885-908, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37245177

RESUMO

miRNAs and lncRNAs play a central role in cancer-associated gene regulations. The dysregulated expression of lncRNAs has been reported as a hallmark of cancer progression, acting as an independent prediction marker for an individual cancer patient. The interplay of miRNA and lncRNA decides the variation of tumorigenesis that could be mediated by acting as sponges for endogenous RNAs, regulating miRNA decay, mediating intra-chromosomal interactions, and modulating epigenetic components. This paper focuses on the influence of crosstalk between lncRNA and miRNA on cancer hallmarks such as epithelial-mesenchymal transition, hijacking cell death, metastasis, and invasion. Other cellular roles of crosstalks, such as neovascularization, vascular mimicry, and angiogenesis were also discussed. Additionally, we reviewed crosstalk mechanism with specific host immune responses and targeting interplay (between lncRNA and miRNA) in cancer diagnosis and management.


Assuntos
MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias/genética , Neoplasias/patologia , Neovascularização Patológica/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica
8.
J Colloid Interface Sci ; 633: 383-395, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36462264

RESUMO

The use of amphiphilic block copolymers to generate colloidal delivery systems for hydrophobic drugs has been the subject of extensive research, with several formulations reaching the clinical development stages. However, to generate particles of uniform size and morphology, with high encapsulation efficiency, yield and batch-to-batch reproducibility remains a challenge, and various microfluidic technologies have been explored to tackle these issues. Herein, we report the development and optimization of poly(ethylene glycol)-block-(ε-caprolactone) (PEG-b-PCL) nanoparticles for intravenous delivery of a model drug, sorafenib. We developed and optimized a glass capillary microfluidic nanoprecipitation process and studied systematically the effects of formulation and process parameters, including different purification techniques, on product quality and batch-to-batch variation. The optimized formulation delivered particles with a spherical morphology, small particle size (dH < 80 nm), uniform size distribution (PDI < 0.2), and high drug loading degree (16 %) at 54 % encapsulation efficiency. Furthermore, the stability and in vitro drug release were evaluated, showing that sorafenib was released from the NPs in a sustained manner over several days. Overall, the study demonstrates a microfluidic approach to produce sorafenib-loaded PEG-b-PCL NPs and provides important insight into the effects of nanoprecipitation parameters and downstream processing on product quality.


Assuntos
Nanopartículas , Neoplasias , Humanos , Sorafenibe , Portadores de Fármacos/química , Microfluídica , Reprodutibilidade dos Testes , Poliésteres/química , Polietilenoglicóis/química , Nanopartículas/química , Tamanho da Partícula
9.
ACS Omega ; 7(50): 46843-46848, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36570178

RESUMO

Analogues of benzene-1,3,5-tricarboxamide bearing combinations of different alkyl chains (dodecyl to octadecyl) and ester-linked PEG (polyethylene glycol) chains are shown to self-assemble into either micelles or nanotapes in aqueous solution, depending on the architecture (number of alkyl vs PEG chains). The cytotoxicity to cells is selectively greater for breast cancer cells than fibroblast controls in a dose-dependent manner. The compounds show strong stability, retaining their self-assembled structures at low pH (relevant to acidic tumor conditions) and in buffer and cell culture media.

10.
Antioxidants (Basel) ; 11(7)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35883869

RESUMO

A nanosized food-grade quercetin-loaded nanoemulsion (QNE) system comprising capmul MCM NF (oil) and cremophor RH 40 (surfactant) was developed using a high-speed homogenization technique. The developed QNE was studied for its significant neuroprotective (anti-Parkinsonism) and cytotoxicity (anticancer) effects against Caenorhabditis elegans (C. elegans) strains and human cancer cells, respectively. HR-TEM studies revealed that the QNE was spherical with a mean globule size of ~50 nm. Selected area electron diffraction (SAED) studies results demonstrated that QNE was amorphous. In vivo results show that QNE potentially reduced the α-Syn aggregation, increased mitochondrial and fat content, and improved the lifespan in transgenic C. elegans strain NL5901. QNE significantly downregulated the reactive oxygen species (ROS) levels in wild-type C. elegans strain N2. In vitro results of the MTT assay show that QNE significantly exhibited chemotherapeutic effects in all treated human cancer cells in an order of cytotoxicity: HeLa cells > A549 cells > MIA PaCa-2 cells, based on the IC50 values at 24 h. Conclusively, the QNE showed improved solubility, targetability, and neuroprotective effects against the PD-induced C. elegans model, and also cytotoxicity against human cancer cells and could be potentially used as an anti-Parkinson's or anticancer agent.

11.
Crit Rev Oncol Hematol ; 174: 103675, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35381343

RESUMO

PURPOSE: Cervical cancer (CC), one of the major causes of death of women throughout the world is primarily caused due to Human Papilloma Virus (HPV) 16 and 18. The early region (E) oncoproteins of HPV are associated with the etiopathogenesis and contribute to the progression of cancer. The present article comprehensively discussed the structural organization and biological functions of all E proteins of HPV and their contribution to progression of CC with an intent to decipher the pathological hallmarks and their relationship. Additionally, the role of E proteins in reference to therapeutics will also be presented. METHODS: A systematic search has been carried out for articles published in PubMed database by using combinations of different keywords with Boolean operators (AND, OR, NOT) including cervical cancer, HPV, E proteins, and signaling. RESULTS: From the analysis of literature review, its apparent that E proteins are the major contributor to disease progression. E1, E2, and E4 forms are mainly associated with viral integration, replication, and transcription whereas E6 and E7 act as an oncoprotein and are associated with the progression of cancer. E5 regulates cell proliferation, apoptosis, and facilitates the activity of E6 and E7. Additionally, E proteins were observed associated with numerous cell signaling pathways including PI3K/AKT, Wnt, Notch and reasonably contribute to the initiation of malignancy, cell proliferation, metastasis, and drug resistance. Knowing the role and interplay of each protein in initiation to progression of CC, their therapeutic significance has been elucidated. The present study observations demonstrate that E6 and E7 are the major cause of HPV-mediated CC progression. E1, E2, and E5 also act as a backbone for E6 and E7 and most of the current approaches have targeted E6 and E7 mediated action only. CONCLUSION: The present review illustrates the structural organization as well as function and regulation of all early proteins of HPV and their association with several cellular signaling pathways. The observations provide clue on the regulatory aspect of these proteins in initiation to progression and reasonably represent that targeting these proteins could be a novel therapeutic strategy for CC. In particular, its seemingly appears that inhibition of the activity of E6 and E7 oncoproteins may be a better selective target to delay the progression of CC. The review reaffirms the role of E proteins and encourages future studies on developing diagnostics, and most importantly therapeutics strategies targeting E6 and E7 oncoproteins to tackle CC related morbidity and mortality.


Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Papillomavirus Humano 16 , Humanos , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus , Fosfatidilinositol 3-Quinases , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
12.
Semin Cancer Biol ; 86(Pt 2): 1086-1104, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35218902

RESUMO

Recent mounting evidence has revealed extensive genetic heterogeneity within tumors that drive phenotypic variation affecting key cancer pathways, making cancer treatment extremely challenging. Diverse cancer types display resistance to treatment and show patterns of relapse following therapy. Therefore, efforts are required to address tumor heterogeneity by developing a broad-spectrum therapeutic approach that combines targeted therapies. Inflammation has been progressively documented as a vital factor in tumor advancement and has consequences in epigenetic variations that support tumor instigation, encouraging all the tumorigenesis phases. Increased DNA damage, disrupted DNA repair mechanisms, cellular proliferation, apoptosis, angiogenesis, and its incursion are a few pro-cancerous outcomes of chronic inflammation. A clear understanding of the cellular and molecular signaling mechanisms of tumor-endorsing inflammation is necessary for further expansion of anti-cancer therapeutics targeting the crosstalk between tumor development and inflammatory processes. Multiple inflammatory signaling pathways, such as the NF-κB signaling pathway, JAK-STAT signaling pathway, MAPK signaling, PI3K/AKT/mTOR signaling, Wnt signaling cascade, and TGF-ß/Smad signaling, have been found to regulate inflammation, which can be modulated using various factors such as small molecule inhibitors, phytochemicals, recombinant cytokines, and nanoparticles (NPs) in conjugation to phytochemicals to treat cancer. Researchers have identified multiple targets to specifically alter inflammation in cancer therapy to restrict malignant progression and improve the efficacy of cancer therapy. siRNA-and shRNA-loaded NPs have been observed to downregulate STAT3 signaling pathways and have been employed in studies to target tumor malignancies. This review highlights the pathways involved in the interaction between tumor advancement and inflammatory progression, along with the novel approaches of nanotechnology-based drug delivery systems currently used to target inflammatory signaling pathways to combat cancer.


Assuntos
Nanomedicina , Fosfatidilinositol 3-Quinases , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Compreensão , Recidiva Local de Neoplasia , Transdução de Sinais , Inflamação/tratamento farmacológico
13.
Cells ; 10(10)2021 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-34685518

RESUMO

Myocardium Infarction (MI) is one of the foremost cardiovascular diseases (CVDs) causing death worldwide, and its case numbers are expected to continuously increase in the coming years. Pharmacological interventions have not been at the forefront in ameliorating MI-related morbidity and mortality. Stem cell-based tissue engineering approaches have been extensively explored for their regenerative potential in the infarcted myocardium. Recent studies on microfluidic devices employing stem cells under laboratory set-up have revealed meticulous events pertaining to the pathophysiology of MI occurring at the infarcted site. This discovery also underpins the appropriate conditions in the niche for differentiating stem cells into mature cardiomyocyte-like cells and leads to engineering of the scaffold via mimicking of native cardiac physiological conditions. However, the mode of stem cell-loaded engineered scaffolds delivered to the site of infarction is still a challenging mission, and yet to be translated to the clinical setting. In this review, we have elucidated the various strategies developed using a hydrogel-based system both as encapsulated stem cells and as biocompatible patches loaded with cells and applied at the site of infarction.


Assuntos
Infarto do Miocárdio/patologia , Miocárdio/citologia , Miócitos Cardíacos/citologia , Regeneração/fisiologia , Células-Tronco/citologia , Diferenciação Celular/fisiologia , Humanos , Infarto do Miocárdio/fisiopatologia , Transplante de Células-Tronco/métodos , Engenharia Tecidual/métodos , Alicerces Teciduais
14.
Antioxidants (Basel) ; 10(8)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34439453

RESUMO

Para-coumaric acid (p-CA) is a plant derived secondary metabolite belonging to the phenolic compounds. It is widely distributed in the plant kingdom and found mainly in fruits, vegetables, and cereals. Various in vivo and in vitro studies have revealed its scavenging and antioxidative properties in the reduction of oxidative stress and inflammatory reactions. This evidence-based review focuses on the protective role of p-CA including its therapeutic potential. p-CA and its conjugates possesses various bioactivities such as antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, and anti-melanogenic properties. Due to its potent free radical scavenging activity, it can mitigate the ill effects of various diseases including arthritis, neurological disorders, and cardio-vascular diseases. Recent studies have revealed that p-CA can ameliorate the harmful effects associated with oxidative stress in the reproductive system, also by inhibiting enzymes linked with erectile function.

15.
Chem Commun (Camb) ; 57(67): 8360-8363, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34338257

RESUMO

The self-assembly in aqueous solution of benzene-1,3,5-tricarboxamide (BTA) bearing one alkyl chain and two PEG (polyethylene glycol) chains or two alkyl chains and one PEG chain yields completely distinct nanostructures. Two series of derivatives were synthesized and extensively characterized and electron microscopy and small-angle X-ray scattering (SAXS) reveal micelle structures for derivatives with one alkyl and two PEG chains, but nanotapes and nanoribbons for the series with two alkyl and one PEG chain.

16.
Int J Pharm ; 607: 121018, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34416329

RESUMO

In this study, novel cupric-tirapazamine [Cu(TPZ)2]-liposomes were developed as an effective hypoxia-targeted therapeutic, which potentiated radiotherapy in a three dimensional (3D) prostate cancer (PCa) model. To overcome the low water solubility of the Cu(TPZ)2, a remote loading method was developed to efficiently load the lipophilic complex into different liposomal formulations. The effect of pH, temperature, PEGylation, lipid composition, liposome size, lipid: complex ratio on the liposome properties, and drug loading was evaluated. The highest loading efficiency was obtained at neutral pH, which was independent of lipid composition and incubation time. In addition, enhanced drug loading was achieved upon decreasing the lipid:complex molar ratio with minimal effects on liposomes' morphology. Interestingly, the in vitro potency of the developed liposomes was easily manipulated by changing the lipid composition. The hydrophilic nature of our liposomal formulations improved the complex's solubility, leading to enhanced cellular uptake and toxicity, both in PCa monolayers and tumour spheroids. Moreover, Cu(TPZ)2-loaded liposomes combined with radiation, showed a significant reduction in PCa spheroids growth rate, compared to the free complex or radiation alone, which could potentiate radiotherapy in patients with localised advanced PCa.


Assuntos
Lipossomos , Neoplasias da Próstata , Humanos , Hipóxia , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Solubilidade , Tirapazamina
17.
Pharmaceuticals (Basel) ; 14(7)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358102

RESUMO

The presence of small subpopulations of cells within tumor cells are known as cancer stem cells (CSCs). These cells have been the reason for metastasis, resistance with chemotherapy or radiotherapy, and tumor relapse in several types of cancers. CSCs underwent to epithelial-mesenchymal transition (EMT) and resulted in the development of aggressive tumors. CSCs have potential to modulate numerous signaling pathways including Wnt, Hh, and Notch, therefore increasing the stem-like characteristics of cancer cells. The raised expression of drug efflux pump and suppression of apoptosis has shown increased resistance with anti-cancer drugs. Among many agents which were shown to modulate these, the plant-derived bioactive agents appear to modulate these key regulators and were shown to remove CSCs. This review aims to comprehensively scrutinize the preclinical and clinical studies demonstrating the effects of phytocompounds on CSCs isolated from various tumors. Based on the available convincing literature from preclinical studies, with some clinical data, it is apparent that selective targeting of CSCs with plants, plant preparations, and plant-derived bioactive compounds, termed phytochemicals, may be a promising strategy for the treatment of relapsed cancers.

18.
Antioxidants (Basel) ; 10(5)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33922139

RESUMO

Reactive oxygen species (ROS) are important in regulating normal cellular processes whereas deregulated ROS leads to the development of a diseased state in humans including cancers. Several studies have been found to be marked with increased ROS production which activates pro-tumorigenic signaling, enhances cell survival and proliferation and drives DNA damage and genetic instability. However, higher ROS levels have been found to promote anti-tumorigenic signaling by initiating oxidative stress-induced tumor cell death. Tumor cells develop a mechanism where they adjust to the high ROS by expressing elevated levels of antioxidant proteins to detoxify them while maintaining pro-tumorigenic signaling and resistance to apoptosis. Therefore, ROS manipulation can be a potential target for cancer therapies as cancer cells present an altered redox balance in comparison to their normal counterparts. In this review, we aim to provide an overview of the generation and sources of ROS within tumor cells, ROS-associated signaling pathways, their regulation by antioxidant defense systems, as well as the effect of elevated ROS production in tumor progression. It will provide an insight into how pro- and anti-tumorigenic ROS signaling pathways could be manipulated during the treatment of cancer.

19.
Cancer Rep (Hoboken) ; 4(4): e1369, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33822486

RESUMO

BACKGROUND: Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three-dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable "super-enzymatic" process that might respond to targeted therapeutic modalities in cancer. RECENT FINDINGS: Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like ßTrcP1 and ßTrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis. CONCLUSION: The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.


Assuntos
Transformação Celular Neoplásica/genética , Proteína 7 com Repetições F-Box-WD/genética , Neoplasias/genética , Mapas de Interação de Proteínas/genética , Receptores Notch/genética , Animais , Modelos Animais de Doenças , Proteína 7 com Repetições F-Box-WD/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Mutação , Neoplasias/mortalidade , Neoplasias/patologia , Fosforilação/genética , Prognóstico , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Receptores Notch/metabolismo , Ubiquitina/metabolismo
20.
Soft Matter ; 17(11): 3096-3104, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33598669

RESUMO

A designed surfactant-like peptide is shown, using a combination of cryogenic-transmission electron microscopy and small-angle X-ray scattering, to have remarkable pH-dependent self-assembly properties. Peptide Arg3-Leu12 (R3L12) forms a network of peptide nanotubes at pH 9 and below. These are associated with α-helical conformation in a "cross-α" nanotube structure, in which peptide dimers lie perpendicular to the nanotube axis, with arginine coated inner and outer nanotube walls. In contrast, this peptide forms decorated vesicular aggregates at higher pH values, close to the pKa of the arginine residues. These structures are associated with a loss of α-helical order as detected through X-ray scattering, circular dichroism and FTIR spectroscopy, the latter technique also revealing a loss of ordering of leucine side chains. This suggests a proposed model for the decorated or patchy vesicular structures that comprises disordered peptide as the matrix of the membrane, with small domains of ordered peptide dimers forming the minority domains. We ascribe this to a lipid-raft like phase separation process, due to conformational disordering of the leucine hydrophobic chains. The observation of the self-assembly of a simple surfactant-like peptide into these types of nanostructure is remarkable, and peptide R3L12 shows unique pH-dependent morphological and conformational behaviour, with the potential for a range of future applications.


Assuntos
Nanoestruturas , Tensoativos , Dicroísmo Circular , Concentração de Íons de Hidrogênio , Peptídeos , Conformação Proteica em alfa-Hélice
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