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1.
Nat Prod Res ; : 1-4, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38164692

RESUMO

The essential oil from Lippia origanoides (EOLO) is employed in traditional medicine as it has both antimicrobial and anti-inflammatory properties. The current investigation first evaluated the EOLO's cytotoxic activity in tumour (SiHa and HT-29) and non-tumour (human lymphocyte) cells by MTT. The effect on ROS production was further evaluated in cancer cells by fluorimetry. The oil's mutagenic and antifungal activities were also evaluated using, respectively, the in vitro micronucleus test and the broth microdilution method. The EOLO displayed significant cytotoxicity in both cancer cell lines, with IC50 values of 20.2 µg/mL and 24.3 µg/mL for HT-29 and for SiHa cell lines, respectively. EOLO increased ROS production, was unable to raise the micronucleus frequencies and significantly reduced the cytokinesis block proliferation indices, revealing its anti-proliferative action. The results demonstrate that EOLO is devoid of mutagenic activity but possesses significant activity against tumour and non-tumour human cells, reinforcing its biological potential.

2.
Medicina (Kaunas) ; 59(12)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38138165

RESUMO

Background and Objectives: Cancer is the second-most-important deadly disease in the world, leading to severe socioeconomic consequences and posing a public threat. Consequently, breast and colorectal cancers are significant cancer types that affect women and men more commonly, respectively. Treatment failure or recurrent diseases frequently occur due to resistance, in addition to the side effects of the currently available anticancer agents. Therefore, in this study, herbal melanin anticancer activity was investigated against human breast adenocarcinoma (MDA-MB-231) and human colorectal (HCT 116) cell proliferation and the expression of downregulated anti-apoptotic proteins and upregulated pro-apoptotic p53. Materials and Methods: MDA-MB-231 and HCT 116 cells were monitored for their real-time proliferation properties using Xcelligence. Herbal melanin of various concentrations significantly inhibited MDA-MB-231 and HCT 116 cell proliferation. Then, the expression of proapoptotic and anti-apoptotic proteins such as p53, Bcl-2 and Bcl-xl was studied using Western blotting. Results: The Bcl-2 and Bcl-xl expressions were downregulated, while the p53 expression was upregulated after treatment with herbal melanin. Similarly, the expression of apoptotic proteins such as Bcl-2, Bcl-xl, XIAP, Survivin, Bid, Bax, p53, Cytochrome C, PARP genes and mRNA was studied after herbal melanin treatment using real-time PCR, which revealed the downregulation of Bcl-2, Bcl-xl, XIAP and Survivin and the upregulation of Bid, Bax, p53, Cytochrome C and PARP apoptotic protein expression. Also, caspase 3 and 9 expressions were monitored after the treatment with herbal melanin, which revealed the upregulation of both the MDA-MB-231 and HCT 116 cell types. Conclusions: Overall, herbal melanin can be used as an alternative anticancer agent against the MDA-MB-231 and HCT 116 cell types.


Assuntos
Antineoplásicos , Neoplasias da Mama , Feminino , Humanos , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/farmacologia , Proteínas Reguladoras de Apoptose/uso terapêutico , Células HCT116 , Proteína Supressora de Tumor p53/genética , Survivina/metabolismo , Survivina/farmacologia , Survivina/uso terapêutico , Melaninas/metabolismo , Melaninas/farmacologia , Melaninas/uso terapêutico , Apoptose , Proteína X Associada a bcl-2/genética , Citocromos c/metabolismo , Citocromos c/farmacologia , Citocromos c/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proliferação de Células , Antineoplásicos/uso terapêutico , Neoplasias da Mama/genética , Linhagem Celular Tumoral
3.
Chemistry ; 29(34): e202203796, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-36892541

RESUMO

The near-infrared (NIR) light-absorbing AgBiS2 nanoparticles can be excited by single-wavelength light, which is the primary characteristic of a photo responsive platform. Chemical synthesis of nanomaterials inevitably requires long-chain organic surfactants or polymers to stabilize them in the nano regime. These stabilizing molecules barricade the interaction of nanomaterials with biological cells. We have produced stabilizer-free (sf-AgBiS2 ) and polymer-coated (PEG-AgBiS2 ) nanoparticles; and assessed their NIR mediated anticancer and antibacterial activity to evaluate the effect of stabilizers. sf-AgBiS2 showed better antibacterial activity against Gram-positive Staphylococcus aureus (S. aureus) and displayed excellent cytotoxicity against HeLa cells and live 3-D tumour spheroids compared to PEG-AgBiS2 both in presence and absence of NIR radiation. The photothermal therapy (PTT) results illustrated the tumour ablation ability of sf-AgBiS2 , which converted light into heat effectively up to 53.3 °C under NIR irradiation. This work demonstrates the importance of synthesizing stabilizer-free nanoparticles to produce safe and highly active PTT agents.


Assuntos
Nanopartículas , Fototerapia , Humanos , Fototerapia/métodos , Células HeLa , Staphylococcus aureus , Nanopartículas/química , Antibacterianos/farmacologia
4.
Molecules ; 28(3)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36770971

RESUMO

Cellular mesenchymal-epithelial transition factor (c-Met), an oncogenic transmembrane receptor tyrosine kinase (RTK), plays an essential role in cell proliferation during embryo development and liver regeneration. Thioredoxin reductase (TrxR) is overexpressed and constitutively active in most tumors closely related to cancer recurrence. Multi-target-directed ligands (MTDLs) strategy provides a logical approach to drug combinations and would adequately address the pathological complexity of cancer. In this work, we designed and synthesized a series of selenium-containing tepotinib derivatives by means of selenium-based bioisosteric modifications and evaluated their antiproliferative activity. Most of these selenium-containing hybrids exhibited potent dual inhibitory activity toward c-Met and TrxR. Among them, compound 8b was the most active, with an IC50 value of 10 nM against MHCC97H cells. Studies on the mechanism of action revealed that compound 8b triggered cell cycle arrest at the G1 phase and caused ROS accumulations by targeting TrxR, and these effects eventually led to cell apoptosis. These findings strongly suggest that compound 8b serves as a dual inhibitor of c-Met and TrxR, warranting further exploitation for cancer therapy.


Assuntos
Antineoplásicos , Selênio , Antineoplásicos/farmacologia , Tiorredoxina Dissulfeto Redutase/metabolismo , Selênio/farmacologia , Piperidinas/farmacologia , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais
5.
Gene ; 853: 147091, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36464168

RESUMO

Management of gastric cancer is still challenging due to resistance to current chemotherapeutics and recurrent disease. Moreover, green- synthesized zinc oxide nanoparticles (ZnO-NPs) using natural resources are one of the most promising therapeutic agents for anticancer therapy. Here we report the facile green synthesis and characterization of ZnO-NPs from Teucrium polium (TP-ZnO-NP) herb extract and the anticancer activities of these nanoparticles on gastric cancer cells. Facile green synthesis of TP-ZnO-NP was achieved using zinc acetate dihydrate. For the characterization of TP-ZnO-NP, UV-vis spectroscopy, FTIR, SEM, XRD and EDX analyses were performed. Antiproliferative and anticancer activities of TP-ZnO-NP were explored using the HGC-27 gastric cancer cell line model. MTT cell viability and colony formation assays were used for the analysis of cell proliferation and migration. Wound healing assay was used to analyze the migration capacities of cells. Annexin V/PI double staining, DNA ladder assay, and Acridine orange/Ethidium bromide staining were performed to analyze the induction of apoptosis. qPCR was used to determine gene expression levels of apoptotic and epithelial to mesenchymal transition marker genes. The aqueous extract of TP served as both a reducing and capping agent for the successful biosynthesis of zinc oxide nanoparticles. Remarkably, synthesized TP-ZnO-NPs were found to have significant antiproliferative and anticancer activities on HGC-27 gastric cancer cells. Collectively, current data suggest that TP-ZnO-NP is a novel and promising anticancer agent for future therapeutic interventions in gastric cancer.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Neoplasias Gástricas , Teucrium , Óxido de Zinco , Humanos , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Óxido de Zinco/metabolismo , Teucrium/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Transição Epitelial-Mesenquimal , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Nanopartículas/química , Apoptose , Transdução de Sinais , Nanopartículas Metálicas/química
6.
Int J Mol Sci ; 23(4)2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35216255

RESUMO

Female breast cancer is the world's most prevalent cancer in 2020. Chemotherapy still remains a backbone in breast cancer therapy and is crucial in advanced and metastatic breast cancer treatment. The clinical efficiency of chemotherapy regimens is limited due to tumor heterogeneity, chemoresistance, and side effects. Chemotherapeutic drug combinations with natural products hold great promise for enhancing their anticancer efficacy. Curcumin is an ideal chemopreventive and chemotherapy agent owning to its multitargeting function on various regulatory molecules, key signaling pathways, and pharmacological safety. This review aimed to elucidate the potential role of curcumin in enhancing the efficacy of doxorubicin, paclitaxel, 5-fluorouracil, and cisplatin via combinational therapy. Additionally, the molecular mechanisms underlying the chemosensitizing activity of these combinations have been addressed. Overall, based on the promising therapeutic potential of curcumin in combination with conventional chemotherapy drugs, curcumin is of considerable value to develop as an adjunct for combination chemotherapy with current drugs to treat breast cancer. Furthermore, this topic may provide the frameworks for the future research direction of curcumin-chemotherapy combination studies and may benefit in the development of a novel therapeutic strategy to maximize the clinical efficacy of anticancer drugs while minimizing their side effects in the future breast cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Curcumina/farmacologia , Animais , Humanos , Transdução de Sinais/efeitos dos fármacos
7.
Cancers (Basel) ; 14(4)2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35205836

RESUMO

Cancer ranks as the first leading cause of death globally. Despite the various types of cancer treatments, negative aspects of the treatments, such as side effects and drug resistance, have been a continuous dilemma for patients. Thus, natural compounds and herbal medicines have earned profound interest as chemopreventive agents for reducing burden for patients. SH003, a novel herbal medicine containing Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii, showed the potential to act as an anticancer agent in previous research studies. A narrative review was conducted to present the significant highlights of the total 15 SH003 studies from the past nine years. SH003 has shown positive results in both in vivo and vitro studies against various types of cancer cells; furthermore, the first clinical trial was performed to identify the maximum tolerated dose among solid cancer patients. So far, the potential of SH003 as a chemotherapeutic agent has been well-documented in research studies; continuous work on SH003's efficacy and safety is required to facilitate better cancer patient care but is part of the knowledge needed to understand whether SH003 has the potential to become a pharmaceutical.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 245: 118946, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32979808

RESUMO

Selenium containing drugs like selenomethionine, selenocystine, selenourea and methylseleninic acid are reported to exhibit potential anticancer effect. However, these anticancer drugs may exert adverse effects when used over a prolonged period. Little is known about the interaction of these selenium containing drugs with the vital erythroid protein hemoglobin. In this work a comparative study of the interaction of organo-selenium drugs with hemoglobin and heme moiety has been performed using different spectroscopic techniques to find out their role on drug induced methemoglobinemia. We found that though these selenium containing drugs have similar binding affinity towards hemoglobin, they have differential interactions with the heme group. Isothermal calorimetric titration study showed that selenourea has the lowest binding affinity (Kd 19.28 µM) towards HbA as compared to other drugs, selenomethionine, selenocystine and methylseleninic acid (Kd 7.69 µM, 4.88 µM and 10.5 µM at 37 °C respectively). This result is also supported by the molecular docking study. Methylseleninic acid was found to have detrimental effects on nitrite induced methemoglobinemia, a hematological disorder caused due to excessive conversion of Fe2+ to Fe3+ in hemoglobin. Hence the results of the study would help to develop a better insight on the mechanism of action and anticipate the toxicity of these drugs which require further optimization before their actual use in the treatment of cancer.


Assuntos
Antineoplásicos , Metemoglobinemia , Compostos Organosselênicos , Selênio , Humanos , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/tratamento farmacológico , Simulação de Acoplamento Molecular , Nitritos , Compostos Organosselênicos/toxicidade
9.
Mini Rev Med Chem ; 21(6): 731-737, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33200707

RESUMO

Cancer is a deadly disease, which has significantly increased in both developed and developing nations. Treatment of cancer utilizing radiotherapy or chemotherapy actuates a few issues which incorporate spewing, sickness, unpalatable reactions, and so forth. In this specific situation, an alternative drug source, which can effectively treat cancer is of prime importance. Products that are obtained from plant sources are utilized for the treatment of various diseases due to their non-harmful nature. Medicinal plants contain different bioactive compounds, which possess an important role in the prevention of different diseases such as cancer. Plumbagin is a bioactive compound, which is mainly present in Plumbaginaceae family and has been explored for its anticancer activity. Plumbagin basically inactivates the Akt/NF-kB, MMP-9 and VEGF pathways that are essential for cancer cell development. Therefore, it is important to review the role of plumbagin in different cancer cells in order to find an alternative drug to overcome this disease. The present review provides a summary of anticancer activity of plumbagin in various cancers and its mode of action.


Assuntos
Antineoplásicos Fitogênicos/química , Naftoquinonas/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Humanos , NF-kappa B/metabolismo , Naftoquinonas/isolamento & purificação , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Plumbaginaceae/química , Plumbaginaceae/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
Molecules ; 25(23)2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33261194

RESUMO

Karwinskia genus consists of shrubs and small trees. Four toxic compounds have been isolated from Karwinskia plants, which were typified as dimeric anthracenones and named T496, T514, T516, and T544. Moreover, several related compounds have been isolated and characterized. Here we review the toxicity of the fruit of Karwinskia plants when ingested (accidentally or experimentally), as well as the toxicity of its isolated compounds. Additionally, we analyze the probable antineoplastic effect of T514. Toxins cause damage mainly to nervous system, liver, lung, and kidney. The pathophysiological mechanism has not been fully understood but includes metabolic and structural alterations that can lead cells to apoptosis or necrosis. T514 has shown selective toxicity in vitro against human cancer cells. T514 causes selective and irreversible damage to peroxisomes; for this reason, it was renamed peroxisomicine A1 (PA1). Since a significant number of malignant cell types contain fewer peroxisomes than normal cells, tumor cells would be more easily destroyed by PA1 than healthy cells. Inhibition of topoisomerase II has also been suggested to play a role in the effect of PA1 on malignant cells. More research is needed, but the evidence obtained so far indicates that PA1 could be an effective anticancer agent.


Assuntos
Antracenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Karwinskia/química , Neoplasias/tratamento farmacológico , Antracenos/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Humanos , Neoplasias/patologia
11.
Int J Biol Macromol ; 162: 1605-1615, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32755706

RESUMO

Over the decades, several nanoparticles have been developed for biomedical applications, still facile green synthesis derived nanoparticles showed tremendous attraction due to avoid of toxic solvent, ease of synthesis and low cost. Here, facile one pot in situ green synthesis is reported to develop silver nanoparticles with the aid of natural polysaccharide presented in sweet lemon peel waste derived carbon dot (CD) acted as a reducing and stabilizing agent at room temperature. The synthesis of CD and CD based silver nanoparticles (CD@AgNPs) was characterized by FTIR, UV-vis spectroscopy, fluorescence spectrophotometer, XRD and TEM. CD@AgNPs exhibited excellent antimicrobial activity against E. coli at very low concentration of 5.0 µg/ml. Interestingly, CD showed selective cytotoxicity against MCF7 breast cancer cells with the IC50 of 10 µg/ml while CD@AgNPs demonstrated synergistic effect on cytotoxicity. It is found that the cells death of MCF7 cells mainly occurred through the up-regulation of intracellular reactive oxygen species (ROS). Therefore, the synthesized CD@AgNPs may show an efficient anticancer agent for targeted breast cancer therapy in future.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Carbono/farmacologia , Química Verde , Extratos Vegetais/farmacologia , Polissacarídeos/química , Prata/farmacologia , Neoplasias da Mama/tratamento farmacológico , Morte Celular/efeitos dos fármacos , Citrus/química , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Frutas/química , Humanos , Células MCF-7 , Nanopartículas Metálicas/química , Pontos Quânticos/química , Espécies Reativas de Oxigênio/metabolismo
12.
Pharm Biol ; 58(1): 490-497, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32478640

RESUMO

Context: Mitrephora sirikitiae Weeras., Chalermglin & R.M.K. Saunders (Annonaceae) is a plant endemic to Thailand. Its constituents and their biological activities are unknown.Objective: Isolation and identification of the compounds in the leaves and stems of M. sirikitiae and determination of their cytotoxicity.Materials and methods: Methanol extracts of the leaves and stems of M. sirikitiae were separated by chromatography, and spectroscopic methods were used to determine the structures of the components. The cytotoxicity of the extracts and pure compounds was evaluated using the sulforhodamine B assay with several cell lines. The cells were treated with the compounds at concentrations of 0.16-20 µg/mL for 48 or 72 h.Results: The investigation of the extracts of M. sirikitiae leaves and stems resulted in the isolation of a new lignan, mitrephoran, and 15 known compounds. Among these compounds, 2-(3,4-dimethoxyphenyl)-6-(3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, ciliaric acid, 6-methoxymarcanine A, and stepharanine were isolated from this genus for the first time. The alkaloids liriodenine and oxoputerine exhibited strong cytotoxicity against all tested cells (IC50 values of 6.59-11.02 µM). In contrast, magnone A, 3',4-O-dimethylcedrusin, and 6-methoxymarcanine A inhibited the growth of some of the tested cells (IC50 values of 2.03-19.73 µM). Magnone A and 6-methoxymarcanine A showed low toxicity for Hek 293 cells (IC50 >20 µM).Discussion and conclusions: M. sirikitiae is a source of cytotoxic lignans and alkaloids. Among the cytotoxic compounds, magnone A and 6-methoxymarcanine A are potentially useful lead compounds for the further development of anticancer agents because of their selective inhibitory effects on cancer cell lines.


Assuntos
Annonaceae , Antineoplásicos Fitogênicos/toxicidade , Citotoxinas/toxicidade , Extratos Vegetais/toxicidade , Folhas de Planta , Células A549 , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Citotoxinas/isolamento & purificação , Relação Dose-Resposta a Droga , Células HEK293 , Células HT29 , Humanos , Células MCF-7 , Extratos Vegetais/isolamento & purificação , Ratos , Espectrometria de Massas por Ionização por Electrospray/métodos , Tailândia
13.
Int J Nanomedicine ; 15: 2935-2945, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425525

RESUMO

BACKGROUND: New anticancer agents that rely on natural/healthy, not synthetic/toxic, components are very much needed. METHODS: Ricinoleyl hydroxamic acid (RHA) was synthesized from castor oil and hydroxylamine using Lipozyme TL IM as a catalyst. To optimize the conversion, the effects of the following parameters were investigated: type of organic solvent, period of reaction, amount of enzyme, the molar ratio of reactants and temperature. The highest conversion was obtained when the reaction was carried out under the following conditions: hexane as a solvent; reaction period of 48 hours; 120 mg of Lipozyme TL IM/3 mmol oil; HA-oil ratio of 19 mmol HA/3 mmol oil; and temperature of 40°C. The cytotoxicity of the synthesized RHA was assessed using human dermal fibroblasts (HDF), and its application towards fighting cancer was assessed using melanoma and glioblastoma cancer cells over a duration of 24 and 48 hours. RESULTS: RHA was successfully synthesized  and it demonstrated strong anticancer activity against glioblastoma and melanoma cells at as low as a 1 µg/mL concentration while it did not demonstrate any toxicity against HDF cells. CONCLUSION: This is the first report on the synthesis of RHA with great potential to be used as a new anticancer agent.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Óleo de Rícino/química , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Catálise , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Hexanos/química , Humanos , Hidroxilamina/química , Lipase/química , Lipase/metabolismo , Melanoma/tratamento farmacológico , Melanoma/patologia , Solventes/química
14.
Molecules ; 25(10)2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32455950

RESUMO

The purpose of this study was to compare the chemical composition and biological properties of Polish propolis. Ethanol, ethanol-hexane, hexane and hexane-ethanol extracts of propolis from three different regions of Poland were prepared. On the basis of the evaluation of their chemical composition as well as the extraction yield and free radical scavenging activity, the ethanol and hexane-ethanol extractions were proposed as the most effective methods. Subsequently, the biological properties of the extracts were evaluated to investigate the selectivity of an anticancer effect on tongue cancer cells in comparison to normal gingival fibroblasts. The obtained products demonstrated anticancer activity against tongue cancer cells. Additionally, when the lowest extract concentration (100 µg/mL) was applied, they were not cytotoxic to gingival fibroblasts. Finally, a possible anti-inflammatory potential of the prepared products was revealed, as reduced mitochondrial activity and proliferation of macrophages exposed to the extracts were observed. The results obtained indicate a potential of Polish propolis as a natural product with cancer-selective toxicity and anti-inflammatory effect. However, further studies are still needed to thoroughly explain the molecular mechanisms of its action and to obtain the promising health benefits of this versatile natural product.


Assuntos
Antineoplásicos/farmacologia , Extratos Vegetais/farmacologia , Própole/química , Neoplasias da Língua/tratamento farmacológico , Antineoplásicos/química , Antioxidantes/química , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/química , Polônia , Própole/farmacologia , Neoplasias da Língua/patologia
15.
Front Oncol ; 10: 325, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32300551

RESUMO

Uveal melanoma (UM) is the most common primary intraocular carcinoma in adults. Cinobufagin, secreted by the Asiatic toad Bufo gargarizans, is a traditional Chinese medicine, widely used in tumor treatment. Here, we explored the potential antitumor function of cinobufagin and investigated its biochemical mechanisms in UM cells. The antitumor potential of cinobufagin was determined via cell viability, cell cycle, and apoptosis assays. Colony formation assays confirmed that cinobufagin exerted potent antitumor activity in a dose-dependent manner. We found that cinobufagin could induce cell apoptosis and upregulate the expression of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase (PARP), and cleaved caspase-9 in vivo and in vitro. In addition, after treatment with increased concentrations of cinobufagin, the intrinsic mitochondrial apoptosis pathway was also activated, which was demonstrated by increased cell apoptosis with increased expression of Bad and Bax, decreased expression of Bcl-2 and Bcl-xl, and reduced mitochondrial membrane potential (MMP) in OCM1 cells. Taken together, the results of this preclinical study suggest that cinobufagin can both inhibit cell survival and induce cell apoptosis in a dose-dependent manner in UM cells, which provides new insights into the biochemical mechanism of cinobufagin and its potential as a future chemotherapeutic agent for UM.

16.
Anticancer Agents Med Chem ; 20(9): 1094-1104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32053085

RESUMO

BACKGROUND: Doxorubicin, as a strong anti-cancer agent for clinical treatment of various cancer types along with other drugs, is widely utilized. Due to the physiology of the human body and cancerous tissues, the applicability of doxorubicin is still limited and the targeted treatment of the different types of cancers is considered. Also, the side effects of the conventional forms of chemotherapy medicines, damaging and stressing the normal cells are considerable. OBJECTIVE: This study introduces a novel and effective system for the targeted release of doxorubicin by successfully fabricating the green magnetic graphene oxide, chitosan, allium sativum, and quercus nanocomposite. METHODS: The in vitro release of doxorubicin loaded on the nanocomposite was evaluated and investigated at pH 7.4 and 6.5, respectively. The drug diffusivity in the plasma environment was assessed for a more accurate analysis of the drug diffusion process. The nanocomposite loaded drug release mechanism and kinetics, as well as cytotoxicity assay was investigated. RESULTS: The efficiency of the drug encapsulation was significantly enhanced using natural extract ingredients and consequently, the efficacy of the targeted treatment of cancerous tissues was improved. The developed nanocomposite provided a controlled release of doxorubicin in similar acidic conditions of the normal and cancerous cells and affirming that the fabricated system is thoroughly pH-dependent. CONCLUSION: The cytotoxicity assay confirmed that the fabricated nanocomposite at a high growth rate of cancerous cells has an anticancer property and acts as a toxic agent against tumor cells, suggesting that in conjunction with doxorubicin, it can be highly improved for killing cancerous cells.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Desenvolvimento de Medicamentos , Nanocompostos/química , Antibióticos Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Relação Dose-Resposta a Droga , Doxorrubicina/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Alho/química , Grafite/química , Humanos , Estrutura Molecular , Quercus/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
17.
Expert Opin Drug Saf ; 18(11): 1009-1015, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31478396

RESUMO

Introduction: Therapeutic drug monitoring in oncology is used to prevent major toxicities of selected anticancer agents due to overexposure by individualizing the dose based on a pharmacokinetic target. Areas covered: Numerous studies relating a relation between pharmacokinetic variability and toxicity have been reported since the eighties but very few have been implemented in clinical practice due to a lack of validation and harmonization, logistical constraints and reluctance from oncologists. Following recent recommendations, this paper highlights the current-validated applications of pharmacokinetic monitoring in oncology focusing on the safety of anticancer therapies. Expert opinion: Paradoxically given the oldness of the agents, guidelines of dose adjustment have been recently available for intravenous busulfan, 5-fluorouracil, and high-dose methotrexate. Interestingly, besides the enhancement of tolerability, it applies to potential curative clinical situations. In an era of personalized oncology that integrates complex molecular factors in the treatment of cancer, education is needed for oncologists to show the benefits of this valuable (even old) resource for the safety of patients. Therapeutic drug monitoring for busulfan, 5-fluorouracil and methotrexate will still hold in the future unless more active agents are available in the concerned indications.


Assuntos
Antineoplásicos/administração & dosagem , Monitoramento de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Bussulfano/farmacocinética , Relação Dose-Resposta a Droga , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/farmacocinética , Humanos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Metotrexato/farmacocinética , Guias de Prática Clínica como Assunto , Medicina de Precisão/métodos
18.
Mar Drugs ; 17(9)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461968

RESUMO

In this paper, the chemical conjugation of marine natural products with other bioactive molecules for developing an advanced anti-cancer agent is described. Structural complexity and the extraordinary biological features of marine natural products have led to tremendous research in isolation, structural elucidation, synthesis, and pharmacological evaluation. In addition, this basic scientific achievement has made it possible to hybridize two or more biologically important skeletons into a single compound. The hybridization strategy has been used to identify further opportunities to overcome certain limitations, such as structural complexity, scarcity problems, poor solubility, severe toxicity, and weak potency of marine natural products for advanced development in drug discovery. Further, well-designed marine chimera molecules can function as a platform for target discovery or degradation. In this review, the design, synthesis, and biological evaluation of recent marine chimera molecules are presented.


Assuntos
Antineoplásicos/síntese química , Organismos Aquáticos/química , Produtos Biológicos/química , Desenho de Fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Produtos Biológicos/farmacologia , Técnicas de Química Sintética/métodos , Avaliação Pré-Clínica de Medicamentos , Humanos , Estrutura Molecular , Neoplasias/tratamento farmacológico , Solubilidade
19.
Int J Nanomedicine ; 14: 4091-4103, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239669

RESUMO

Introduction: Curcuma wenyujin is a plant which belongs to the family of Zingiberaceae, found in South Asia and China. C. wenyujin is a major constituent in Chinese traditional medicine and is used to treat liver diseases, blood clots, and is also prescribed as a painkiller. C. wenyujin possesses antioxidant, antiproliferative, and antitumorogenic properties, and many researchers have proved the efficacy of C. wenyujin against various types of cancer. The major drawback of this historical drug is it's low bioavailability. Methods: This study synthesized gold nanoparticles using C. wenyujin and assessed its potency against in vitro renal cancer cells. The biosynthesized C. wenyujin gold nanoparticles (CWAuNPs) were characterized using UV-Spec, DLS, FTIR, SAED, TEM, EDAX, and Atomic Force analysis. The cytotoxicity of CWAuNPs against renal cancer cell lines A498 and SW-156 was assessed with MTT assay. The induction of apoptosis by CWAuNPs in A498 cell was measured using apoptotic staining DAPI, Rhodamine 123, and H2DCFDA. The apoptotic activity of CWAuNPs was further confirmed with flow cytometric analysis. The molecular mechanism of CWAuNPs was analyzed with qPCR and immunoblotting analysis of caspases, proapoptotic, and antiapoptotic proteins. Results: The characterization of results of synthesized CWAuNPs satisfy the distinctive properties of a potent nanodrug. The results of apoptotic staining techniques confirm the induction of CWAuNPs in A498 by increasing the apoptotic Caspase 3,9, Bid, and Bad, and decreasing the antiapoptotic protein Bcl-2, Bcl-xl expressions, which is authentically proven by the qPCR and immunoblotting analysis. Conclusion: In conclusion, these results confirmed that biosynthesized CWAuNPs is a potent anticancer agent which induces apoptosis in the A498 renal carcinoma cell line.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Curcuma/química , Ouro/farmacologia , Neoplasias Renais/tratamento farmacológico , Nanopartículas Metálicas/química , Extratos Vegetais/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Nanopartículas Metálicas/ultraestrutura , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Biomed Pharmacother ; 109: 1680-1687, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551422

RESUMO

The steady rise in life expectancy, modern life style and changing environmental conditions are responsible for increasing incidence of cancer. A number of chemical drugs have been used for cancer treatment; however the induction of genotoxic, carcinogenic and teratogenic effects limits their use. Alternatively, plant phytochemicals have been proven effective chemopreventive agents. This review illustrates the use of "picrosides" derived from Picrorhiza kurroa for the treatment of cancer. We have detailed the anti-oxidant and anti-inflammatory action of picrosides as the key mechanism in reducing oncogenesis. Action of picrosides on detoxifying enzymes, cell cyle regulation and induction of signal transducers inhibiting apoptosis has also been reviewed. The present review highlights the use of picrosides as an important therapeutic agent against different types of cancer.


Assuntos
Anticarcinógenos/uso terapêutico , Cinamatos/uso terapêutico , Glucosídeos Iridoides/uso terapêutico , Picrorhiza , Plantas Medicinais , Animais , Anticarcinógenos/química , Anticarcinógenos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/uso terapêutico , Cinamatos/química , Cinamatos/isolamento & purificação , Humanos , Glucosídeos Iridoides/química , Glucosídeos Iridoides/isolamento & purificação , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
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