RESUMO
The design of novel polymeric carrier systems with functional coatings is of great interest for delivering various bioactive molecules. Microcapsules coated with polyelectrolyte (PE) films provide additional functionality and fine-tuning advantages essential for controlled drug release. We developed hydrogel microcarriers coated with functional PE films with encapsulated substances of natural origin, resveratrol (RES), curcumin (CUR), and epigallocatechin gallate (EGCG), which have cytotoxic and chemopreventive properties. Alginate (ALG) based microparticles were loaded with phytopharmaceuticals using the emulsification method, and then their surface was modified with PE coatings, such as chitosan (CHIT) or poly(allylamine hydrochloride) (PAH). The morphology and mean diameter of microcarriers were characterised by scanning electron microscopy, encapsulation efficiency was determined by UV-Vis spectroscopy, whereas the physicochemical properties of functional PE layers were studied using quartz crystal microbalance with dissipation monitoring and streaming potential measurements. The release profiles of active compounds from the hydrogel microparticles were described using the Peppas-Sahlin model. The cytotoxic effect of designed delivery systems was studied by evaluating their impact on the proliferation, mitochondrial metabolic function, and lipid peroxidation level of 5637 human bladder cancer cells. The present work demonstrates that the physicochemical and biological features of fabricated microcarriers can be controlled by the type of encapsulated anti-cancer agent and PE coating.
Assuntos
Alginatos , Antineoplásicos , Humanos , Polieletrólitos/química , Alginatos/química , Hidrogéis , Polímeros , ResveratrolRESUMO
Regulated cell death is an essential and heterogeneous process occurring in the life cycle of organisms, from embryonic development and aging to the regulation of homeostasis and organ maintenance. Under this term, we can distinguish many distinct pathways, including apoptosis and pyroptosis. Recently, there has been an increasing comprehension of the mechanisms governing these phenomena and their characteristic features. The coexistence of different types of cell death and the differences and similarities between them has been the subject of many studies. This review aims to present the latest literature in the field of pyroptosis and apoptosis and compare their molecular pathway's elements and significance in the physiology and pathophysiology of the organism.
Assuntos
Apoptose , Piroptose , Apoptose/fisiologia , Morte CelularRESUMO
This paper aims to overview different types of stress, including DNA replication stress, oxidative stress, and psychological stress. Understanding the processes that constitute a cellular response to varied types of stress lets us find differences in how normal cells and cancer cells react to the appearance of a particular kind of stressor. The revealed dissimilarities are the key for targeting new molecules and signaling pathways in anticancer treatment. For this reason, molecular mechanisms that underlay DNA replication stress, oxidative stress, and psychological stress have been studied and briefly presented to indicate biochemical points that make stressors contribute to cancer development. What is more, the viewpoint in which cancer constitutes the outcome and the cause of stress has been taken into consideration. In a described way, this paper draws attention to the problem of cancer-related post-traumatic stress disorder and proposes a novel, multidimensional oncological approach, connecting anticancer treatment with psychiatric support.
Assuntos
Transtornos de Estresse Pós-Traumáticos , Carcinogênese/genética , Humanos , Estresse Oxidativo/fisiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Estresse Psicológico/genéticaRESUMO
BACKGROUND: Although cardioplegia is used since the '70s of the last century, debate on cardioprotection during cardio-surgical procedures is still actual. The selection of a particular method depends mainly on the preferences and experience of a specific center or even surgeon. Crystalloid cardioplegia is an aqueous ion solution similar to intracellular (Custodiol HTK) or extracellular (Plegisol) fluid. The potensional clinical advantages of relatively new idea of cardioplegia solution based on intracellular composition (Custodiol HTK) justifies futher research, but only a few used cultured cells in laboratory conditions. METHODS: In this study, the authors sought to compare Custodiol HTK with Plegisol cardioplegia solutions using an in-vitro model simulating cardioplegic arrest. The efficacy of myocardial protection during ischemia was investigated with susceptible indicators like the appearance of the deleterious effect of reactive oxygen species and oxidative stress markers. Immersed human cardiomyocytes and rat cardiomyoblasts H9C2 in cardioplegia for 4 h were examined for expression of oxidative stress markers (MnSOD, iNOS, HSP27), cardioplegic solutions cytotoxicity, and peroxidation damage of the cell's lipids and proteins. All tests were performed after 0.5 h, 1 h, 2 h, and 4 h of incubation in identical physical and biological conditions, which is difficult to achieve in clinical trials. RESULTS: The lower cytotoxicity index performed on matured cells of human cardiomyocytes and highest dehydrogenase level showed after incubation with Custodiol HTK. This did not apply to tests on immature cells H9C2. Custodiol HTK induced significantly stronger iNOS expression. The decrease of HSP27 concentration has been instantaneous and maintained troughout the study only in both cultures incubated with Custodiol HTK. The other tests: lipid peroxidation, carbonyl groups concentration and MnSOD expression show no clear superiority evidence of used cardioplegic solutions. CONCLUSIONS: Considering proceeded examinations on cultured cardiomyocytes, Custodiol HTK appears to be safer than Plegisol.
Assuntos
Soluções Cardioplégicas , Miócitos Cardíacos , Animais , Bicarbonatos , Cloreto de Cálcio , Soluções Cardioplégicas/uso terapêutico , Soluções Cardioplégicas/toxicidade , Glucose/farmacologia , Glucose/uso terapêutico , Proteínas de Choque Térmico HSP27 , Parada Cardíaca Induzida/efeitos adversos , Humanos , Magnésio , Cloreto de Potássio , Ratos , Estudos Retrospectivos , Cloreto de SódioRESUMO
Occupational and environmental exposure to xenoestrogens, a subgroup of endocrine disruptors (EDCs), can affect the endocrine system and increase the risk of cancer, primarily the hormone-dependent kind. This type of cancer includes ovarian cancer, which is the leading cause of death from gynecological tumors. The aim of this study was to assess the role of 17ß-estradiol and its metabolites: 2-MeOE2, 16α-OHE1 in exposure to the metalloestrogen cadmium. The effect of interactions of cadmium with estrogens on the viability of cells in malignant ovarian cancer cells SKOV-3 was investigated, both in simultaneous action and in the pre-incubation model. There are no known interactions between estrogens and cadmium in ovarian cancer cells. Due to the frequent occurrence of multidrug resistance (MDR) in ovarian cancer, the effects of estrogens and cadmium on MDR in SKOV-3, measured as P-glycoprotein (P-gp), were assessed. An interaction study showed that E2 had an antagonistic effect on cadmium-induced cell damage, while 2-MeOE2 showed less of a protective effect in combination with CdCl2 than E2. There were two types of interaction: toxic synergism and beneficial antagonism. E2 and cadmium increased P-gp expression in SKOV-3 cells, while 2-MeOE2 decreased P-gp expression to a potentially beneficial effect on MDR prevention. The obtained results constitute an interesting starting point for further research in the field of interactions between estrogens and xenoestrogens in ovarian cancer.
Assuntos
Cádmio , Neoplasias Ovarianas , 2-Metoxiestradiol , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Cádmio/metabolismo , Carcinoma Epitelial do Ovário , Linhagem Celular , Estradiol/metabolismo , Estrogênios/metabolismo , Humanos , Neoplasias Ovarianas/tratamento farmacológicoRESUMO
(1) Background: The size and surface charge are the most significant parameters of nanocarriers that determine their efficiency and potential application. The poor cell uptake of encapsulated drugs is the main limitation in anticancer treatment. The well-defined properties of nanocarriers will enable to target specific tissue and deliver an active cargo. (2) Methods: In the current study, poly(D,L -lactide) (PLA) nanocarriers loaded with curcumin (CUR) and differing surface charge were evaluated for transport efficacy in combination with electroporation (EP) in dependence on the type of cells. The obtained CUR-loaded nanoparticles with diameters ranging from 195 to 334 nm (derived from dynamic light scattering (DLS)) were characterized by atomic force microscopy (AFM) (morphology and shape) and Doppler electrophoresis (ζ-potential) as well as UV-vis spectroscopy (CUR encapsulation efficiency (about 90%) and photobleaching rate). The drug delivery properties of the obtained PLA nanocarriers enhanced by electroporation were assessed in human colon cancer cells (LoVo), excitable normal rat muscle cells (L6), and free of voltage-gated ion channels cells (CHO-K1). CLSM studies, viability, and ROS release were performed to determine the biological effects of nanocarriers. (3) Results: The highest photodynamic activity indicated anionic nanocarriers (1a) stabilized by C12(COONa)2 surfactant. Nanocarriers were cytotoxic for LoVo cells and less cytotoxic for normal cells. ROS release increased in cancer cells with the increasing electric field intensity, irradiation, and time after EP. Muscle L6 cells were less sensitive to electric pulses. (4) Conclusions: EP stimulation for CUR-PLA nanocarriers transport was considered to improve the regulated and more effective delivery of nanosystems differing in surface charge.
Assuntos
Neoplasias do Colo/tratamento farmacológico , Curcumina/química , Curcumina/farmacologia , Nanopartículas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Células CHO , Linhagem Celular , Linhagem Celular Tumoral , Cricetulus , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Eletroporação/métodos , Humanos , Tamanho da Partícula , RatosRESUMO
Cancer is one of the greatest challenges in modern medicine today. Difficult and long-term treatment, the many side effects of the drugs used and the growing resistance to treatment of neoplastic cells necessitate new approaches to therapy. A very promising targeted therapy is based on direct impact only on cancer cells. As a continuation of our research on new biologically active molecules, we report herein the design, synthesis and anticancer evaluation of a new series of N-Mannich-base-type hybrid compounds containing morfoline or different substituted piperazines moieties, a 1,3,4-oxadiazole ring and a 4,6-dimethylpyridine core. All compounds were tested for their potential cytotoxicity against five human cancer cell lines, A375, C32, SNB-19, MCF-7/WT and MCF-7/DX. Two of the active N-Mannich bases (compounds 5 and 6) were further evaluated for growth inhibition effects in melanoma (A375 and C32), and normal (HaCaT) cell lines using clonogenic assay and a population doubling time test. The apoptosis was determined with the neutral version of comet assay. The confocal microscopy method enabled the visualization of F-actin reorganization. The obtained results demonstrated that compounds 5 and 6 have cytotoxic and proapoptotic effects on melanoma cells and are capable of inducing F-actin depolarization in a dose-dependent manner. Moreover, computational chemistry approaches, molecular docking and electrostatic potential were employed to study non-covalent interactions of the investigated compounds with four receptors. It was found that all the examined molecules exhibit a similar binding affinity with respect to the chosen reference drugs.
Assuntos
Antineoplásicos , Melanoma , Actinas , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Bases de Mannich/química , Bases de Mannich/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Oxidiazóis , Piperazinas/farmacologia , Relação Estrutura-AtividadeRESUMO
Gynecological carcinomas affect an increasing number of women and are associated with poor prognosis. The gold standard treatment plan is mainly based on surgical resection and subsequent chemotherapy with cisplatin, 5-fluorouracil, anthracyclines, or taxanes. Unfortunately, this treatment is becoming less effective and is associated with many side effects that negatively affect patients' physical and mental well-being. Electroporation based on tumor exposure to electric pulses enables reduction in cytotoxic drugs dose while increasing their effectiveness. EP-based treatment methods have received more and more interest in recent years and are the subject of a large number of scientific studies. Some of them show promising therapeutic potential without using any cytotoxic drugs or molecules already present in the human body (e.g., calcium electroporation). This literature review aims to present the fundamental mechanisms responsible for the course of EP-based therapies and the current state of knowledge in the field of their application in the treatment of gynecological neoplasms.
Assuntos
Antineoplásicos , Neoplasias da Mama , Eletroquimioterapia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/etiologia , Cisplatino/uso terapêutico , Eletroquimioterapia/métodos , Eletroporação/métodos , Feminino , HumanosRESUMO
(1) Background: Pulsed electric field (PEF) techniques are commonly used to support the delivery of various molecules. A PEF seems a promising method for low permeability drugs or when cells demonstrate therapy resistance and the cell membrane becomes an impermeable barrier. (2) Methods: In this study, we have used doxorubicin-resistant and sensitive models of human breast cancer (MCF-7/DX, MCF-7/WT) and colon cancer cells (LoVo, LoVoDX). The study aimed to investigate the susceptibility of the cells to doxorubicin (DOX) and electric fields in the 20-900 ns pulse duration range. The viability assay was utilized to evaluate the PEF protocols' efficacy. Cell confluency and reduced glutathione were measured after PEF protocols. (3) Results: The obtained results showed that PEFs significantly supported doxorubicin delivery and cytotoxicity after 48 and 72 h. The 60 kV/cm ultrashort pulses × 20 ns × 400 had the most significant cytotoxic anticancer effect. The increase in DOX concentration provokes a decrease in cell viability, affected cell confluency, and reduced GSSH when combined with the ESOPE (European Standard Operating Procedures of Electrochemotherapy) protocol. Additionally, reactive oxygen species after PEF and PEF-DOX were detected. (4) Conclusions: Ultrashort electric pulses with low DOX content or ESOPE with higher DOX content seem the most promising in colon and breast cancer treatment.
Assuntos
Neoplasias da Mama , Neoplasias do Colo , Eletroquimioterapia , Neoplasias da Mama/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Doxorrubicina/uso terapêutico , Resistência a Medicamentos , Resistencia a Medicamentos Antineoplásicos , Eletroquimioterapia/métodos , Eletroporação/métodos , Feminino , HumanosRESUMO
Breast cancer is one of the most common malignant neoplasms, and despite the dynamic development of anticancer therapies, 5-year survival in the metastatic stage is still less than 30%. 6-Gingerol (1-[4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone) is a substance contained in ginger, which exhibits anti-cancer properties. Paclitaxel is a cytostatic substance used to treat breast cancer, but its therapeutically effective dose has many adverse effects. The aim of the presented study was to assess the anticancer effect of 6-gingerol and the possibility of increasing the effectiveness of Paclitaxel in the death induction of wild type human breast cancer cells. MCF-7/WT cells were treated with drugs-6-gingerol and paclitaxel at selected concentrations. The mitochondrial activity assay, caspase 7 activity assay, ATP assay, microscopy studies, and RT-PCR assays were performed to evaluate the antitumor activity and mechanism of action of both compounds, alone and in combination. After 72 h of incubation, the mitochondrial activity showed that the combination of 5 nM Paclitaxel with 10 µM 6-Gingerol led to the same decrease in viability as the use of 20 nM Paclitaxel alone; 10 µM 6-Gingerol led to an enhancement of caspase 7 activity, with the highest activity observed after 24 h of incubation. A real-time PCR study showed that 6-Gingerol induces the simultaneous transcription of Bax with TP53 genes in large excess to BCL-2. In contrast, 5 nM Paclitaxel induces TP53 transcription in excess of BCL-2 and Bax. Our results suggest that 6-Gingerol may act as a cell death-inducing agent in cancer cells and, in combination with paclitaxel, and increase the effectiveness of conventional chemotherapy.
Assuntos
Adenocarcinoma , Neoplasias da Mama , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Caspase 7 , Catecóis , Linhagem Celular Tumoral , Álcoois Graxos , Feminino , Humanos , Paclitaxel , Proteína X Associada a bcl-2RESUMO
Background and Objectives: The cardioplegic arrest of the heart during cardiosurgical procedures is the crucial element of a cardioprotection strategy. Numerous clinical trials compare different cardioplegic solutions and cardioprotective protocols, but a relatively small number of papers apply to in vitro conditions using cultured cells. This work aimed to analyze whether it is possible to use the rat heart myocardium cells as an in vitro model to study the protective properties of St. Thomas cardioplegia (ST2C). Methods: The rat heart myocardium cells-H9C2 were incubated with cold cardioplegia for up to 24 h. After incubation, we determined: viability, confluency, and cell size, the thiol groups' level by modifying Ellman's method, Ki67, and Proliferating Cell Nuclear Antigen expression (PCNA). The impact on cells' morphology was visualized by the ultrastructural (TEM) study and holotomograpic 3D imaging. Results: The viability and confluency analysis demonstrated that the safest exposure to ST2C, should not exceed 4h. An increased expression of Ki67 antigen and PCNA was observed. TEM and 3D imaging studies revealed vacuolization after the longest period of exposure (24). Conclusions: According to obtained results, we conclude that STC can play a protective role in cardiac surgery during heart arrest.
Assuntos
Parada Cardíaca Induzida , Miocárdio , Animais , Soluções Cardioplégicas/química , Soluções Cardioplégicas/metabolismo , Soluções Cardioplégicas/farmacologia , Coração , Parada Cardíaca Induzida/métodos , Mioblastos , Miocárdio/metabolismo , RatosRESUMO
Natural killer (NK) cells are key innate immunity effectors that combat viral infections and control several cancer types. For their immune function, human NK cells rely largely on five different cytotoxic proteases, called granzymes (A/B/H/K/M). Granzyme B (GrB) initiates at least three distinct cell death pathways, but key aspects of its function remain unexplored because selective probes that detect its activity are currently lacking. In this study, we used a set of unnatural amino acids to fully map the substrate preferences of GrB, demonstrating previously unknown GrB substrate preferences. We then used these preferences to design substrate-based inhibitors and a GrB-activatable activity-based fluorogenic probe. We show that our GrB probes do not significantly react with caspases, making them ideal for in-depth analyses of GrB localization and function in cells. Using our quenched fluorescence substrate, we observed GrB within the cytotoxic granules of human YT cells. When used as cytotoxic effectors, YT cells loaded with GrB attacked MDA-MB-231 target cells, and active GrB influenced its target cell-killing efficiency. In summary, we have developed a set of molecular tools for investigating GrB function in NK cells and demonstrate noninvasive visual detection of GrB with an enzyme-activated fluorescent substrate.
Assuntos
Corantes Fluorescentes/química , Granzimas , Imagem Óptica , Peptídeos/química , Linfócitos T/enzimologia , Linhagem Celular Tumoral , Granzimas/química , Granzimas/metabolismo , HumanosRESUMO
The application of ginkgolides as a herbal remedy reaches ancient China. Over time many studies confirmed the neuroprotective effect of standard Ginkgo biloba tree extract-the only available ginkgolide source. Ginkgolides present a wide variety of neuroregulatory properties, commonly used in the therapy process of common diseases, such as Alzheimer's, Parkinson's, and many other CNS-related diseases and disorders. The neuroregulative properties of ginkgolides include the conditioning of neurotransmitters action, e.g., glutamate or dopamine. Besides, natural compounds induce the inhibition of platelet-activating factors (PAF). Furthermore, ginkgolides influence the inflammatory process. This review focuses on the role of ginkgolides as neurotransmitters or neuromodulators and overviews their impact on the organism at the molecular, cellular, and physiological levels. The clinical application of ginkgolides is discussed as well.
Assuntos
Ginkgolídeos/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Animais , Biomarcadores , Estudos Clínicos como Assunto , Gerenciamento Clínico , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Ginkgo biloba/química , Ginkgolídeos/química , Ginkgolídeos/uso terapêutico , Humanos , Imunomodulação/efeitos dos fármacos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Neurotransmissores/química , Neurotransmissores/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Resultado do TratamentoRESUMO
Neoplastic diseases are still a major medical challenge, requiring a constant search for new therapeutic options. A serious problem of many cancers is resistance to anticancer drugs and disease progression in metastases or local recurrence. These characteristics of cancer cells may be related to the specific properties of cancer stem cells (CSC). CSCs are involved in inhibiting cells' maturation, which is essential for maintaining their self-renewal capacity and pluripotency. They show increased expression of transcription factor proteins, which were defined as stemness-related markers. This group of proteins includes OCT4, SOX2, KLF4, Nanog, and SALL4. It has been noticed that the metabolism of cancer cells is changed, and the demand for iron is significantly increased. Iron chelators have been proven to have antitumor activity and influence the expression of stemness-related markers, thus reducing chemoresistance and the risk of tumor cell progression. This prompts further investigation of these agents as promising anticancer novel drugs. The article presents the characteristics of stemness markers and their influence on the development and course of neoplastic disease. Available iron chelators were also described, and their effects on cancer cells and expression of stemness-related markers were analyzed.
Assuntos
Quelantes de Ferro/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Electroporation is influenced by the features of the targeted cell membranes, e.g., the cholesterol content and the surface tension of the membrane. The latter is eventually affected by the organization of actin fibers. Atorvastatin is a statin known to influence both the cholesterol content and the organization of actin. This work analyzes the effects of the latter on the efficacy of electroporation of cancer cells. In addition, herein, electroporation was combined with calcium chloride (CaEP) to assess as well the effects of the statin on the efficacy of electrochemotherapy. Cholesterol-rich cell lines MDA-MB231, DU 145, and A375 underwent (1) 48 h preincubation or (2) direct treatment with 50 nM atorvastatin. We studied the impact of the statin on cholesterol and actin fiber organization and analyzed the cells' membrane permeability. The viability of cells subjected to PEF (pulsed electric field) treatments and CaEP with 5 mM CaCl2 was examined. Finally, to assess the safety of the therapy, we analyzed the N-and E-cadherin localization using confocal laser microscopy. The results of our investigation revealed that depending on the cell line, atorvastatin preincubation decreases the total cholesterol in the steroidogenic cells and induces reorganization of actin nearby the cell membrane. Under low voltage PEFs, actin reorganization is responsible for the increase in the electroporation threshold. However, when subject to high voltage PEF, the lipid composition of the cell membrane becomes the regulatory factor. Namely, preincubation with atorvastatin reduces the cytotoxic effect of low voltage pulses and enhances the cytotoxicity and cellular changes induced by high voltage pulses. The study confirms that the surface tension regulates of membrane permeability under low voltage PEF treatment. Accordingly, to reduce the unfavorable effects of preincubation with atorvastatin, electroporation of steroidogenic cells should be performed at high voltage and combined with a calcium supply.
Assuntos
Antineoplásicos/farmacologia , Atorvastatina/farmacologia , Cálcio/metabolismo , Colesterol/metabolismo , Eletroquimioterapia/métodos , Eletroporação/métodos , Neoplasias/terapia , Anticolesterolemiantes/farmacologia , Apoptose , Membrana Celular , Permeabilidade da Membrana Celular , Proliferação de Células , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Células Tumorais CultivadasRESUMO
This study aimed to characterize the hydrogel micro- and macro-particles designed to deliver curcumin to human colon cancer cells (LoVo). Six series of vehicles based on sodium alginate (micro- and macro-particles, uncoated, coated with chitosan or gelatin) were synthesized. The uncoated microparticles were fabricated using an emulsion-based technique and the uncoated macroparticles with an extrusion technique, with both coupled with ionotropic gelation. The surface morphology of the particles was examined with scanning electron microscopy and the average size was measured. The encapsulation efficiency, moisture content, and swelling index were calculated. The release of curcumin from the particles was studied in an experiment simulating the conditions of the stomach, intestine, and colon. To evaluate the anticancer properties of such targeted drug delivery systems, the cytotoxicity of both curcumin-loaded and unloaded carriers to human colon cancer cells was assessed. The microparticles encapsulated much less of the payload than the macroparticles and released their content in a more prolonged manner. The unloaded carriers were not cytotoxic to LoVo cells, while the curcumin-loaded vehicles impaired their viability-more significantly after incubation with microparticles compared to macroparticles. Gelatin-coated or uncoated microparticles were the most promising carriers but their potential anticancer activity requires further thorough investigation.
Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Curcumina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Alginatos/química , Alginatos/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Quitosana/química , Quitosana/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Gelatina/química , Gelatina/farmacologia , Humanos , Microesferas , Tamanho da PartículaRESUMO
Modifications of the composition or organization of the cancer cell membrane seem to be a promising targeted therapy. This approach can significantly enhance drug uptake or intensify the response of cancer cells to chemotherapeutics. There are several methods enabling lipid bilayer modifications, e.g., pharmacological, physical, and mechanical. It is crucial to keep in mind the significance of drug resistance phenomenon, ion channel and specific receptor impact, and lipid bilayer organization in planning the cell membrane-targeted treatment. In this review, strategies based on cell membrane modulation or reorganization are presented as an alternative tool for future therapeutic protocols.
Assuntos
Membrana Celular , Sistemas de Liberação de Medicamentos , Neoplasias , Membrana Celular/metabolismo , Membrana Celular/patologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
Natural polymers have been commonly applied in medicine and pharmacy. Their primary function is to enhance drug delivery, tissue regeneration or wound healing, and diagnostics. Natural polymers appear promising for photodynamic protocols, including photodiagnosis (PDD) and photodynamic therapy (PDT). Currently, the most challenging issue with natural polymers is to appropriately select the most effective material regarding the type of cancer treated. The technological achievements enable functionalization of natural polymers by specific antibodies, or enhancement using fluorescent or quantum dot markers for diagnostic applications. This review will discuss the types and properties of natural polymers and available applications of PDD and PDT which seem to be promising in cancer treatment. Treatment of neoplastic diseases is still a challenge for both physicians and scientists, so the search for alternative methods of treatment and diagnosis based on natural materials is relevant.
Assuntos
Neoplasias , Fotoquimioterapia , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , PolímerosRESUMO
Vanicosides A and B are the esters of hydroxycinnamic acids with sucrose, occurring in a few plant species from the Polygonaceae family. So far, vanicosides A and B have not been evaluated for anticancer activity against human malignant melanoma. In this study, we tested these two natural products, isolated from Reynoutria sachalinensis rhizomes, against two human melanoma cell lines (amelanotic C32 cell line and melanotic A375 cell line, both bearing endogenous BRAFV600E mutation) and two normal human cell lines-keratinocytes (HaCaT) and the primary fibroblast line. Additionally, a molecular docking of vanicoside A and vanicoside B with selected targets involved in melanoma progression was performed. Cell viability was studied using an MTT assay. A RealTime-Glo™ Annexin V Apoptosis and Necrosis assay was used for monitoring programmed cell death (PCD). Vanicoside A demonstrated strong cytotoxicity against the amelanotic C32 cell line (viability of the C32 cell line was decreased to 55% after 72 h incubation with 5.0 µM of vanicoside A), significantly stronger than vanicoside B. This stronger cytotoxic activity can be attributed to an additional acetyl group in vanicoside A. No significant differences in the cytotoxicity of vanicosides were observed against the less sensitive A375 cell line. Moreover, vanicosides caused the death of melanoma cells at concentrations from 2.5 to 50 µM, without harming the primary fibroblast line. The keratinocyte cell line (HaCaT) was more sensitive to vanicosides than fibroblasts, showing a clear decrease in viability after incubation with 25 µM of vanicoside A as well as a significant phosphatidylserine (PS) exposure, but without a measurable cell death-associated fluorescence. Vanicosides induced an apoptotic death pathway in melanoma cell lines, but because of the initial loss of cell membrane integrity, an additional cell death mechanism might be involved like permeability transition pore (PTP)-mediated necrosis that needs to be explored in the future. Molecular docking indicated that both compounds bind to the active site of the BRAFV600E kinase and MEK-1 kinase; further experiments on their specific inhibitory activity of these targets should be considered.
Assuntos
Cinamatos/farmacologia , Melanoma/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cinamatos/metabolismo , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma Amelanótico/tratamento farmacológico , Melanoma Amelanótico/patologia , Simulação de Acoplamento Molecular , Extratos Vegetais/farmacologia , Polygonaceae/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Rizoma/químicaRESUMO
The rhizome of Anemarrhena asphodeloides Bunge, used in Traditional Chinese Medicine as a brain function-improving herb, is a promising source of neuroprotective substances. The aim of this study was to evaluate the protective action of xanthones from A. asphodeloides rhizomes on the PC12 cell line exposed to the neurotoxic agent-3-nitropropionic acid (3-NP). The xanthone-enriched fraction of the ethanolic extract of A. asphodeloides (abbreviated from now on as XF, for the Xanthone Fraction), rich in polyphenolic xanthone glycosides, in concentrations from 5 to 100 µg/mL, and 3-NP in concentrations from 2.5 to 15 mM, were examined. After 8, 16, 24, 48, and 72 h of exposure of cells to various combinations of 3-NP and XF, the MTT viability assay was performed and morphological changes were estimated by confocal fluorescence microscopy. The obtained results showed a significant increase in the number of cells surviving after treatment with XF with exposure to neurotoxic 3-NP and decreased morphological changes in PC12 cells in a dose and time dependent manner. The most effective protective action was observed when PC12 cells were pre-incubated with the XF. This effect may contribute to the traditional indications of this herb for neurological and cognitive complaints. However, a significant cytotoxicity observed at higher XF concentrations (over 10 µg/mL) and longer incubation time (48 h) requires caution in future research and thorough investigation into potential adverse effects.