RESUMO
In vitro alternative therapy of human epidermoid squamous carcinoma (A431) by superparamagnetic hyperthermia (SPMHT) using Fe3O4 (magnetite) superparamagnetic nanoparticles (SPIONs) with an average diameter of 15.8 nm, bioconjugated with hydroxypropyl gamma-cyclodextrins (HP-γ-CDs) by means of polyacrylic acid (PAA) biopolymer, is presented in this paper. The therapy was carried out at a temperature of 43 °C for 30 min using the concentrations of Fe3O4 ferrimagnetic nanoparticles from nanobioconjugates of 1, 5, and 10 mg/mL nanoparticles in cell suspension, which were previously found by us to be non-toxic for healthy cells (cell viabilities close to 100%), according to ISO standards (cell viability must be greater than 70%). The temperature for the in vitro therapy was obtained by the safe application (without exceeding the biological limit and cellular damage) of an alternating magnetic field with a frequency of 312.4 kHz and amplitudes of 168, 208, and 370 G, depending on the concentration of the magnetic nanoparticles. The optimal concentration of magnetic nanoparticles in suspension was found experimentally. The results obtained after the treatment show its high effectiveness in destroying the A431 tumor cells, up to 83%, with the possibility of increasing even more, which demonstrates the viability of the SPMHT method with Fe3O4-PAA-(HP-γ-CDs) nanobioconjugates for human squamous cancer therapy.
Assuntos
Carcinoma de Células Escamosas , Hipertermia Induzida , Nanopartículas de Magnetita , Neoplasias Cutâneas , gama-Ciclodextrinas , Humanos , Hipertermia Induzida/métodos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , gama-Ciclodextrinas/química , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Sobrevivência Celular/efeitos dos fármacos , Nanoconjugados/químicaRESUMO
The current study focuses on the synthesis via combustion of dysprosium-doped cobalt ferrites that were subsequently physicochemically analyzed in terms of morphological and magnetic properties. Three types of doped nanoparticles were prepared containing different Dy substitutions and coated with HPGCD for higher dispersion properties and biocompatibility, and were later submitted to biological tests in order to reveal their potential anticancer utility. Experimental data obtained through FTIR, XRD, SEM and TEM confirmed the inclusion of Dy3+ ions in the nanoparticles' structure. The size of the newly formed nanoparticles ranged between 20 and 50 nm revealing an inverse proportional relationship with the Dy content. Magnetic studies conducted by VSM indicated a decrease in remanent and saturation mass magnetization, respectively, in Dy-doped nanoparticles in a direct proportionality with the Dy content; the decrease was further amplified by cyclodextrin complexation. Biological assessment in the presence/absence of red light revealed a significant cytotoxic activity in melanoma (A375) and breast (MCF-7) cancer cells, while healthy keratinocytes (HaCaT) remained generally unaffected, thus revealing adequate selectivity. The investigation of the underlying cytotoxic molecular mechanism revealed an apoptotic process as indicated by nuclear fragmentation and shrinkage, as well as by Western blot analysis of caspase 9, p53 and cyclin D1 proteins. The anticancer activity for all doped Co ferrites varied was in a direct correlation to their Dy content but without being affected by the red light irradiation.
Assuntos
Antineoplásicos , Neoplasias da Mama , Melanoma , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Células MCF-7 , Nanopartículas/química , Luz , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo , Melanoma/tratamento farmacológicoRESUMO
Triterpenic compounds stand as a widely investigated class of natural compounds due to their remarkable therapeutic potential. However, their use is currently being hampered by their low solubility and, subsequently, bioavailability. In order to overcome this drawback and increase the therapeutic use of triterpenes, cyclodextrins have been introduced as water solubility enhancers; cyclodextrins are starch derivatives that possess hydrophobic internal cavities that can incorporate lipophilic molecules and exterior surfaces that can be subjected to various derivatizations in order to improve their biological behavior. This review aims to summarize the most recent achievements in terms of triterpene:cyclodextrin inclusion complexes and bioconjugates, emphasizing their practical applications including the development of new isolation and bioproduction protocols, the elucidation of their underlying mechanism of action, the optimization of triterpenes' therapeutic effects and the development of new topical formulations.
Assuntos
Ciclodextrinas/química , Desenho de Fármacos , Desenvolvimento de Medicamentos , Triterpenos/química , Triterpenos/farmacologia , Fenômenos Químicos , Ciclodextrinas/classificação , Composição de Medicamentos , Humanos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Relação Estrutura-Atividade , Triterpenos/isolamento & purificaçãoRESUMO
The last decade has witnessed a sustained increase in the research development of modern-day chemo-therapeutics, especially for those used for high mortality rate pathologies. However, the therapeutic landscape is continuously changing as a result of the currently existing toxic side effects induced by a substantial range of drug classes. One growing research direction driven to mitigate such inconveniences has converged towards the study of natural molecules for their promising therapeutic potential. Triterpenes are one such class of compounds, intensively investigated for their therapeutic versatility. Although the pharmacological effects reported for several representatives of this class has come as a well-deserved encouragement, the pharmacokinetic profile of these molecules has turned out to be an unwelcomed disappointment. Nevertheless, the light at the end of the tunnel arrived with the development of nanotechnology, more specifically, the use of liposomes as drug delivery systems. Liposomes are easily synthesizable phospholipid-based vesicles, with highly tunable surfaces, that have the ability to transport both hydrophilic and lipophilic structures ensuring superior drug bioavailability at the action site as well as an increased selectivity. This study aims to report the results related to the development of different types of liposomes, used as targeted vectors for the delivery of various triterpenes of high pharmacological interest.
Assuntos
Lipossomos/química , Triterpenos/administração & dosagem , Ensaios Clínicos como Assunto , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas , Triterpenos/químicaRESUMO
Pentacyclic triterpenes, such as betulinic, ursolic, and oleanolic acids are efficient and selective anticancer agents whose underlying mechanisms of action have been widely investigated. The introduction of N-bearing heterocycles (e.g., triazoles) into the structures of natural compounds (particularly pentacyclic triterpenes) has yielded semisynthetic derivatives with increased antiproliferative potential as opposed to unmodified starting compounds. In this work, we report the synthesis and biological assessment of benzotriazole esters of betulinic acid (BA), oleanolic acid (OA), and ursolic acid (UA) (compounds 1-3). The esters were obtained in moderate yields (28-42%). All three compounds showed dose-dependent reductions in cell viability against A375 melanoma cells and no cytotoxic effects against healthy human keratinocytes. The morphology analysis of treated cells showed characteristic apoptotic changes consisting of nuclear shrinkage, condensation, fragmentation, and cellular membrane disruption. rtPCR analysis reinforced the proapoptotic evidence, showing a reduction in anti-apoptotic Bcl-2 expression and upregulation of the pro-apoptotic Bax. High-resolution respirometry studies showed that all three compounds were able to significantly inhibit mitochondrial function. Molecular docking showed that compounds 1-3 showed an increase in binding affinity against Bcl-2 as opposed to BA, OA, and UA and similar binding patterns compared to known Bcl-2 inhibitors.
Assuntos
Ácido Oleanólico , Triterpenos , Apoptose , Linhagem Celular Tumoral , Ésteres/farmacologia , Humanos , Simulação de Acoplamento Molecular , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Triterpenos Pentacíclicos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2 , Triazóis/farmacologia , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Clinical trials have evidenced that several natural compounds, belonging to the phytochemical classes of alkaloids, terpenes, phenols and flavonoids, are effective for the management of various types of cancer. Latest research has proven that natural products and their semisynthetic variants may serve as a starting point for new drug candidates with a diversity of biological and pharmacological activities, designed to improve bioavailability, overcome cellular resistance, and enhance therapeutic efficacy. This review was designed to bring an update regarding the anticancer potential of betulonic acid and its semisynthetic derivatives. Chemical derivative structures of betulonic acid including amide, thiol, and piperidine groups, exert an amplification of the in vitro anticancer potential of betulonic acid. With the need for more mechanistic and in vivo data, some derivatives of betulonic acids may represent promising anticancer agents.
Assuntos
Antineoplásicos/química , Ácido Oleanólico/análogos & derivados , Animais , Antineoplásicos/uso terapêutico , Humanos , Ácido Oleanólico/química , Ácido Oleanólico/uso terapêuticoRESUMO
Melanoma represents one of the most aggressive and drug resistant skin cancers with poor prognosis in its advanced stages. Despite the increasing number of targeted therapies, novel approaches are needed to counteract both therapeutic resistance and the side effects of classic therapy. Betulinic acid (BA) is a bioactive phytocompound that has been reported to induce apoptosis in several types of cancers including melanomas; however, its effects on mitochondrial bioenergetics are less investigated. The present study performed in A375 human melanoma cells was aimed to characterize the effects of BA on mitochondrial bioenergetics and cellular behavior. BA demonstrated a dose-dependent inhibitory effect in both mitochondrial respiration and glycolysis in A375 melanoma cells and at sub-toxic concentrations (10 µM) induced mitochondrial dysfunction by eliciting a decrease in the mitochondrial membrane potential and changes in mitochondria morphology and localization. In addition, BA triggered a dose-dependent cytotoxic effect characterized by apoptotic features: morphological alterations (nuclear fragmentation, apoptotic bodies) and the upregulation of pro-apoptotic markers mRNA expression (Bax, Bad and Bak). BA represents a viable therapeutic option via a complex modulatory effect on mitochondrial metabolism that might be useful in advanced melanoma or as reliable strategy to counteract resistance to standard therapy.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Melanócitos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Triterpenos Pentacíclicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Regulação da Expressão Gênica , Glicólise/efeitos dos fármacos , Glicólise/genética , Humanos , Concentração Inibidora 50 , Melanócitos/metabolismo , Melanócitos/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/agonistas , Transdução de Sinais , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/genética , Proteína de Morte Celular Associada a bcl/metabolismo , Ácido BetulínicoRESUMO
Despite the recent advances in the field of chemically synthetized pharmaceutical agents, nature remains the main supplier of bioactive molecules. The research of natural products is a valuable approach for the discovery and development of novel biologically active compounds possessing unique structures and mechanisms of action. Although their use belongs to the traditional treatment regimes, plant-derived compounds still cover a large portion of the current-day pharmaceutical agents. Their medical importance is well recognized in the field of oncology, especially as an alternative to the limitations of conventional chemotherapy (severe side effects and inefficacy due to the occurrence of multi-drug resistance). This review offers a comprehensive perspective of the first blockbuster chemotherapeutic agents of natural origin's (e.g. taxol, vincristine, doxorubicin) mechanism of action using 3D representation. In addition is portrayed the step-by-step evolution from preclinical to clinical evaluation of the most recently studied natural compounds with potent antitumor activity (e.g. resveratrol, curcumin, betulinic acid, etc.) in terms of anticancer mechanisms of action and the possible indications as chemotherapeutic or chemopreventive agents and sensitizers. Finally, this review describes several efficient platforms for the encapsulation and targeted delivery of natural compounds in cancer treatment.
Assuntos
Antineoplásicos/farmacologia , Terapias Complementares , Descoberta de Drogas , Plantas/química , Animais , Antineoplásicos/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Quimioprevenção , Humanos , Modelos MolecularesRESUMO
Melissa officinalis (MO) is a medicinal plant well-known for its multiple pharmacological effects, including anti-inflammatory, anticancer and beneficial effects on skin recovery. In this context, the present study was aimed to investigate the in vitro and in vivo safety profile of an MO aqueous extract by assessing cell viability on normal (HaCaT-human keratinocytes) and tumor (A375-human melanoma) cells and its impact on physiological skin parameters by a non-invasive method. In addition, the antioxidant activity and the antiangiogenic potential of the extract were verified. A selective cytotoxic effect was noted in A375 cells, while no toxicity was noticed in healthy cells. The MO aqueous extract safety profile after topical application was investigated on SKH-1 mice, and an enhanced skin hydration and decreased erythema and transepidermal water loss levels were observed. The in ovo CAM assay, performed to investigate the potential modulating effect on the angiogenesis process and the blood vessels impact, indicated that at concentrations of 100 and 500 µg/mL, MO aqueous extract induced a reduction of thin capillaries. No signs of vascular toxicity were recorded at concentrations as high as 1000 µg/mL. The aqueous extract of MO leaves can be considered a promising candidate for skin disorders with impaired physiological skin parameters.
Assuntos
Antioxidantes/química , Melissa/química , Extratos Vegetais/química , Pele/metabolismo , Animais , Antioxidantes/uso terapêutico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Plantas Medicinais/química , Pele/efeitos dos fármacosRESUMO
The antimycobacterial investigation of azepanobetulin and its amide derivative was performed. Both compounds showed increased in vitro antibacterial activity on the H37Rv MTB strain in aerobic and anaerobic conditions. Basing on differences between MIC and IC50 values a predominant bactericidal effect for amide in contrast to azepanobetulin with a bacteriostatic antibacterial mechanism is defined. Both compounds showed a strong antibacterial effect against resistant MTB strains with amide derivative being slightly more active. Amide derivative also showed a higher antibacterial potency against non-tuberculous mycobacterial strains (M. avium, M. abscessus). Molecular docking studies showed that the inhibition of tuberculosinyl adenosine transferase (Rv3378c) could constitute an antimycobacterial mechanism of action for these triterpenic azepane derivatives. The pharmacokinetic profile was evaluated by ADMET studies and azepanobetulin showing the better results was evaluated by in vivo experiments. This compound has demonstrated a statistically significant antimycobacterial activity compared to control, but inferior to isoniazid. Our findings show that pentacyclic triterpene derivatives holding a seven-membered azepane A-ring are the promising template for the development of new agents with high antibacterial potential against M. tuberculosis H37Rv, non-tuberculous mycobacterial and drug- resistant strains.
Assuntos
Amidas/farmacologia , Antibacterianos/farmacologia , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Simulação de Acoplamento Molecular , Mycobacterium/efeitos dos fármacos , Amidas/síntese química , Amidas/química , Antibacterianos/síntese química , Antibacterianos/química , Inibidores das Enzimas do Citocromo P-450/síntese química , Inibidores das Enzimas do Citocromo P-450/química , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Células THP-1RESUMO
Origanum vulgare L. is a widely used aromatic plant, especially due to its content in essential oil, mainly rich in carvacrol and thymol. The ethnopharmacological uses of Origanum vulgare L. essential oil (OEO) comprise digestive, respiratory, or dermatological disorders. The review focuses on the increasing number of recent studies investigating several biological activities of OEO. The bioactivities are in tight relation to the phytochemical profile of the essential oil, and also depend on taxonomic, climatic, and geographical characteristics of the plant material. The antibacterial, antifungal, antiparasitic, antioxidant, anti-inflammatory, antitumor, skin disorders beneficial effects, next to antihyperglycemic and anti-Alzheimer activities were reported and confirmed in multiple studies. Moreover, recent studies indicate a positive impact on skin disorders of OEO formulated as nanocarrier systems in order to improve its bioavailability and, thus, enhancing its therapeutic benefits. The review brings an up to date regarding the phytochemistry and bioactivity of Origanum vulgare L. essential oil, underlining also the most successful pharmaceutical formulation used for skin disorders.
Assuntos
Óleos Voláteis/farmacologia , Origanum/química , Compostos Fitoquímicos/farmacologia , Dermatopatias/tratamento farmacológico , Animais , HumanosRESUMO
Albendazole is a benzimidazole derivative with documented antitumor activity and low toxicity to healthy cells. The major disadvantage in terms of clinical use is its low aqueous solubility which limits its bioavailability. Albendazole was incorporated into stable and homogeneous polyurethane structures with the aim of obtaining an improved drug delivery system model. Spectral and thermal analysis was used to investigate the encapsulation process and confirmed the presence of albendazole inside the nanoparticles. The in vitro anticancer properties of albendazole encapsulated in polyurethane structures versus the un-encapsulated compound were tested on two breast cancer cell lines, MCF-7 and MDA-MB-231, in terms of cellular viability and apoptosis induction. The study showed that the encapsulation process enhanced the antitumor activity of albendazole on the MCF-7 and MDA-MB-23 breast cancer lines. The cytotoxic activity manifested in a concentration-dependent manner and was accompanied by changes in cell morphology and nuclear fragmentation.
Assuntos
Albendazol , Antineoplásicos , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos , Nanopartículas , Albendazol/química , Albendazol/farmacocinética , Albendazol/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Feminino , Humanos , Células MCF-7 , Nanopartículas/química , Nanopartículas/uso terapêuticoRESUMO
Wounds are among the most common skin conditions, displaying a large etiological diversity and being characterized by different degrees of severity. Wound healing is a complex process that involves multiple steps such as inflammation, proliferation and maturation and ends with scar formation. Since ancient times, a widely used option for treating skin wounds are plant- based treatments which currently have become the subject of modern pharmaceutical formulations. Triterpenes with tetracyclic and pentacyclic structure are extensively studied for their implication in wound healing as well as to determine their molecular mechanisms of action. The current review aims to summarize the main results of in vitro, in vivo and clinical studies conducted on lupane, ursane, oleanane, dammarane, lanostane and cycloartane type triterpenes as potential wound healing treatments.
Assuntos
Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/uso terapêutico , Cicatrização/efeitos dos fármacos , Animais , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Conformação Molecular , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Pele/anatomia & histologia , Dermatopatias/tratamento farmacológico , Dermatopatias/etiologia , Dermatopatias/patologia , Fenômenos Fisiológicos da Pele , Relação Estrutura-Atividade , Resultado do TratamentoRESUMO
Cannabis sativa L. is a plant long used for its textile fibers, seed oil, and oleoresin with medicinal and psychoactive properties. It is the main source of phytocannabinoids, with over 100 compounds detected so far. In recent years, a lot of attention has been given to the main phytochemicals present in Cannabis sativa L., namely, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Compared to THC, CBD has non-psychoactive effects, an advantage for clinical applications of anti-tumor benefits. The review is designed to provide an update regarding the multi-target effects of CBD in different types of cancer. The main focus is on the latest in vitro and in vivo studies that present data regarding the anti-proliferative, pro-apoptotic, cytotoxic, anti-invasive, anti-antiangiogenic, anti-inflammatory, and immunomodulatory properties of CBD together with their mechanisms of action. The latest clinical evidence of the anticancer effects of CBD is also outlined. Moreover, the main aspects of the pharmacological and toxicological profiles are given.
Assuntos
Antineoplásicos/uso terapêutico , Canabidiol/uso terapêutico , Cannabis/química , Neoplasias/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Humanos , PrognósticoRESUMO
In this study Fe3O4@C matrix was obtained by combustion method and used hereafter as adsorbent for paracetamol and acetylsalicylic acid removal from aqueous solutions. The Fe3O4@C matrix was characterized by electronic microscopy, X-ray diffraction, thermal analysis, Fourier-transform infrared spectroscopy, and magnetic measurements. Two kinetic models of pseudo first-order and pseudo-second-order for both paracetamol and acetylsalicylic acid were studied. The experimental data were investigated by Langmuir, Freundlich, and Redlich-Peterson adsorption isotherm models. The adsorption followed the Redlich-Peterson and pseudo-second-order models with correlation coefficients R2 = 0.98593 and R2 = 0.99996, respectively, for the adsorption of paracetamol; for the acetylsalicylic acid, the adsorption followed the Freundlich and pseudo-second-order model, with correlation coefficients R2 = 0.99421 and R2 = 0.99977, respectively. The equilibrium was quickly reached after approximately 1h for the paracetamol adsorption and approximately 2h for acetylsalicylic acid adsorption. According to the Langmuir isotherm, the maximum adsorption capacity of the magnetic matrix was 142.01 mg·g-1 for the retention of paracetamol and 234.01 mg·g-1 for the retention of acetylsalicylic acid. The benefits of using the Fe3O4@C matrix are the low cost of synthesis and its easy and fast separation from solution by using an NdBFe magnet.
Assuntos
Acetaminofen/química , Aspirina/química , Óxido Ferroso-Férrico/síntese química , Poluentes Químicos da Água/química , Adsorção , Óxido Ferroso-Férrico/química , Cinética , Microscopia Eletrônica , Modelos Químicos , Espectroscopia de Infravermelho com Transformada de Fourier , Água/química , Purificação da Água/métodos , Difração de Raios XRESUMO
The link between melanoma development and the use of oral combined contraceptives is not fully elucidated, and the data concerning this issue are scarce and controversial. In the present study, we show that the components of oral contraceptives, ethinylestradiol (EE), levonorgestrel (LNG), and their combination (EE + LNG) ± UVB (ultraviolet B radiation) induced differential effects on healthy (human keratinocytes, fibroblasts, and primary epidermal melanocytes, and murine epidermis cells) and melanoma cells (human-A375 and murine-B164A5), as follows: (i) at low doses (1 µM), the hormones were devoid of significant toxicity on healthy cells, but in melanoma cells, they triggered cell death via apoptosis; (ii) higher doses (10 µM) were associated with cytotoxicity in all cells, the most affected being the melanoma cells; (iii) UVB irradiation proved to be toxic for all types of cells; (iv) UVB irradiation + hormonal stimulation led to a synergistic cytotoxicity in the case of human melanoma cells-A375 and improved viability rates of healthy and B164A5 cells. A weak irritant potential exerted by EE and EE + LNG (10 µM) was assessed by the means of a chick chorioallantoic membrane assay. Further studies are required to elucidate the hormones' cell type-dependent antimelanoma effect and the role played by melanin in this context.
Assuntos
Anticoncepcionais/efeitos adversos , Etinilestradiol/efeitos adversos , Levanogestrel/efeitos adversos , Melanoma/etiologia , Pele/efeitos dos fármacos , Animais , Apoptose , Linhagem Celular , Linhagem Celular Tumoral , Anticoncepcionais/toxicidade , Etinilestradiol/toxicidade , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Levanogestrel/toxicidade , Melanócitos/efeitos dos fármacos , Melanócitos/efeitos da radiação , Melanoma/metabolismo , Camundongos , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversosRESUMO
Chamomile, parsley, and celery represent major botanical sources of apigenin, a well-known flavone with chemopreventive properties. The aim of this study was to assess the phytochemical composition, antioxidant, and anti-inflammatory potential of methanol extracts obtained from chamomile, parsley, and celery collected from Romania, as well as the biological activity against A375 human melanoma and human dendritic cells. Results have shown that all three extracts are rich in polyphenolic compounds and flavonoids, and they generate a radical scavenger capacity, iron chelation potential, as well as lipoxygenase inhibition capacity. Chamomile and celery extracts present weak antiproliferative and pro-apoptotic properties in the set experimental conditions, while parsley extract draws out significant pro-apoptotic potential against A375 human melanoma cells. Parsley and chamomile extracts affected the fibroblast-like morphology of the screened tumor cell line. On the other hand, chamomile and celery extracts abrogated the expansion of LPS-activated dendritic cells, while the metabolic activity was attenuated by stimulation with celery extract; chamomile and parsley extracts had no effect upon this parameter. Chamomile and parsley extracts incubation with naive dendritic cells did not trigger cytokine secretion (TNF-alpha, IL-6, IL-10), but celery extract stimulation significantly reduced the anti-inflammatory, cytokine IL-10.
Assuntos
Apium/química , Camomila/química , Células Dendríticas/efeitos dos fármacos , Melanoma/patologia , Petroselinum/química , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Flavonoides/farmacologia , Sequestradores de Radicais Livres/farmacologia , Humanos , Inibidores de Lipoxigenase/farmacologia , Extratos Vegetais/análise , Polifenóis/análise , Polifenóis/farmacologia , Proteína Supressora de Tumor p53/metabolismoRESUMO
Ephedra alata Decne. belongs to the Ephedraceae family. It is a species of Ephedra that grows mostly in the desert. Today, the main importance of Ephedra species in the medical field is due to the presence of the alkaloids derived from phenyl-alanine, which act on the sympathetic nervous system as a sympathomimetic. The aim of this study was to conduct a phytochemical characterization of the hydroalcoholic extract of the aerial part of Ephedra alata Decne., which is indigenous to Tunis, that involves the total phenolic content, individual phenolic content, and antioxidant activity as well as a biological screening for the evaluation of the antimicrobial, antifungal, antiproliferative, pro-apoptotic, and cytotoxic potential against the MCF-7 breast cancer cell line. The results show that the hydroalcoholic extract contains polyphenolic phytocompounds (156.226 ± 0.5 mgGAE/g extract) and elicits antioxidant activity (7453.18 ± 2.5 µmol Trolox/g extract). The extract acted as a bacteriostatic agent against all tested bacterial strains, but was bactericidal only against the Gram-positive cocci and Candida spp. In the set experimental parameters, the extract presents antiproliferative, pro-apoptotic, and cytotoxic potential against the MCF-7 human breast cancer cell line.
Assuntos
Antibacterianos/química , Anti-Infecciosos/química , Antioxidantes/química , Ephedra/química , Extratos Vegetais/química , Antibacterianos/farmacologia , Humanos , Células MCF-7 , Extratos Vegetais/farmacologia , Polifenóis/química , Polifenóis/farmacologiaRESUMO
Products of natural origin have become important agents in the treatment of cancer, and the active principles of natural sources could be used in combination with chemotherapeutic agents to increase their effects and to minimize their toxicity. Oleanolic (OA) and ursolic (UA) acids are intensely studied for their promising anticancer potential. The aim of this study was focused on the in vitro toxicological effects induced by UA and OA human mesenchymal stem cells and on melanoma, one of the most frequent cancers whose incidence is increasing every year. The two compounds were tested for their cytotoxic, cell cycle arrest and pro-apoptotic effects on melanoma cells (A375 and B164A5) and mesenchymal stem cells. UA exerted a cytotoxic effect in a dose-dependent manner on melanoma cells, while OA's activity has been shown to be low or moderate. Both compounds produced alterations of the cell cycle, arresting cells in the G0/G1 phase. Furthermore, UA induced significant apoptosis through the bcl-2 genes family pathway, with the decrease of the bcl-2 gene expression. The two compounds exerted selective effects on melanoma cells with no effects on human mesenchymal stem cells. The presented results reveal the anticancer potential of UA on melanoma cells, with no detectable toxicity on the mesenchymal stem cells.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Melanoma/tratamento farmacológico , Ácido Oleanólico/farmacologia , Triterpenos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes bcl-2/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Ácido UrsólicoRESUMO
CONTEXT: Oleanolic and ursolic acids are antitumor and antibacterial agents which are extensively studied. Their major disadvantage is the poor water solubility which limits their applications. OBJECTIVES: Oleanolic and ursolic acid were encapsulated into polyurethane nanostructures that act as drug carriers. In order to evaluate the effectiveness of the particles, anti-microbial and anti-proliferative activity compared to un-encapsulated active compounds was tested. MATERIALS AND METHODS: Using an interfacial polycondensation technique, combined with spontaneous emulsification, structures with nanoscale dimensions were obtained. Scanning electron microscopy, differential scanning calorimetry and X-ray assays confirmed the encapsulation process. Concentrations of 10 and 30 µM particles and un-encapsulated compounds were tested by MTT viability assay for several breast cancer lines, with an exposure time of 72 h. For the antibacterial studies, the dilution method with MIC determination was used. RESULTS: Ursolic acid had an excellent inhibitory effect with IC50 value of 2.47, 1.20, 1.26 and 1.34 µM on MCF7, T47D, MDA-MB-231 and MDA-MB-361, respectively. Oleanolic acid did not show anti-proliferative activity. The pure compounds showed their antibacterial activity only against Bacillus species and Candida albicans, but MIC values were too high to be considered efficient antimicrobial agents (2280 and 4570 µg mL - 1, respectively). Polyurethane nanoparticles which incorporated the agents did not show any biological activity. DISCUSSION AND CONCLUSION: Although the active compounds did not fully exert their anti-proliferative activity following encapsulation inside polymeric nanoparticles, in vivo evaluation is needed in order to obtain an exhaustive conclusion, as the active compounds could be released as a result of metabolic activity.