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Introduction: There is an unmet need to develop potent therapeutics against cancer with minimal side effects and systemic toxicity. Thymol (TH) is an herbal medicine with anti-cancer properties that has been investigated scientifically. This study shows that TH induces apoptosis in cancerous cell lines such as MCF-7, AGS, and HepG2. Furthermore, this study reveals that TH can be encapsulated in a Polyvinyl alcohol (PVA)-coated niosome (Nio-TH/PVA) to enhance its stability and enable its controlled release as a model drug in the cancerous region. Materials and Methods: TH-loaded niosome (Nio-TH) was fabricated and optimized using Box-Behnken method and the size, polydispersity index (PDI) and entrapment efficiency (EE) were characterized by employing DLS, TEM and SEM, respectively. Additionally, in vitro drug release and kinetic studies were performed. Cytotoxicity, antiproliferative activity, and the mechanism were assessed by MTT assay, quantitative real-time PCR, flow cytometry, cell cycle, caspase activity evaluation, reactive oxygen species investigation, and cell migration assays. Results: This study demonstrated the exceptional stability of Nio-TH/PVA at 4 °C for two months and its pH-dependent release profile. It also showed its high toxicity on cancerous cell lines and high compatibility with HFF cells. It revealed the modulation of Caspase-3/Caspase-9, MMP-2/MMP-9 and Cyclin D/ Cyclin E genes by Nio-TH/PVA on the studied cell lines. It confirmed the induction of apoptosis by Nio-TH/PVA in flow cytometry, caspase activity, ROS level, and DAPI staining assays. It also verified the inhibition of metastasis by Nio-TH/PVA in migration assays. Conclusion: Overall, the results of this study revealed that Nio-TH/PVA may effectively transport hydrophobic drugs to cancer cells with a controlled-release profile to induce apoptosis while exhibiting no detectable side effects due to their biocompatibility with normal cells.
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Neoplasias , Álcool de Polivinil , Humanos , Álcool de Polivinil/química , Timol/farmacologia , Lipossomos , Cinética , Linhagem CelularRESUMO
Drug resistance of cancer cells is a major issue in cancer treatment. Plant-mediated nanoparticle synthesis has been applied in recent years to overcome this problem. In this study, the biogenic synthesis of AuNPs was explored using Satureja rechingeri Jamzad aqueous leaf extract, and their anticancer effects were evaluated in cisplatin-resistant A2780CP ovarian cancer cells. The chemical composition of S. rechingeri Jamzad was analyzed using gas chromatography-mass spectrometry. The characteristics of green-synthesized AuNPs were confirmed using XRD, FTIR, UV-visible spectroscopy, TEM, SEM, EDX, DLS, and zeta potential. The cytotoxic effects of AuNPs and S. rechingeri Jamzad aqueous extract on cisplatin-resistant A2780CP ovarian cancer cells were evaluated by MTT assay and flow cytometry. Real-time PCR analyzed gene expression. The chemical composition revealed that carvacrol (89%) was the main component of the S. rechingeri Jamzad extract. The average size of the spherical biosynthesized AuNPs was 15.1 ± 3.7 nm. The AuNPs and plant extract inhibited the growth of cisplatin-resistant ovarian cancer cells in a time- and dose-dependent manner. The apoptotic cell death was confirmed by flow cytometry and DAPI staining. The proapoptotic genes were upregulated, while anti-apoptotic and metastatic genes were downregulated. According to the cell cycle analysis, cancer cells were arrested in the G0/G1 phase. Considering the anticancer activity of the synthesized AuNPs using S. rechingeri Jamzad and the low side effects of AuNPs on normal cells, these AuNPs showed strong potential for use as biological agents in drug-resistant cancer cells treatment.
Assuntos
Antineoplásicos , Nanopartículas Metálicas , Neoplasias Ovarianas , Satureja , Humanos , Feminino , Cisplatino/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Química VerdeRESUMO
Targeted drug delivery and increasing the biological activity of drugs is one of the recent challenges of pharmaceutical researchers. Niosomes are one of the new targeted drug delivery systems that enhances the biological properties of drugs. In this study, for the first time, the green synthesis of selenium nanoparticles (SeNPs), and its loading into niosome was carried out to increase the anti-bacterial and anti-cancer activity of SeNPs. Different formulations of noisome-loaded SeNPs were prepared, and the physical and chemical characteristics of the prepared niosomes were investigated. The antibacterial and anti-biofilm effects of synthesized niosomes loaded SeNPs and free SeNPs against standard pathogenic bacterial strains were studied, and also its anticancer activity was investigated against breast cancer cell lines. The expression level of apoptotic genes in breast cancer cell lines treated with niosome-loaded SeNPs and free SeNPs was measured. Also, to evaluate the biocompatibility of the synthesized niosomes, their cytotoxicity effects against the human foreskin fibroblasts normal cell line (HFF) were studied using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The results illustrated that the optimal formulation had an average size of 177.9 nm, a spherical shape, and an encapsulation efficiency of 37.58%. Also, the results revealed that the release rate of SeNPs from niosome-loaded SeNPs and free SeNPs was 61.26% and 100%, respectively, in 72 h. Also, our findings demonstrated that the niosome-loaded SeNPs have significant antibacterial, anti-biofilm, and anticancer effects compared to the free SeNPs. In addition, niosome-loaded SeNPs can upregulate the expression level of Bax, cas3, and cas9 apoptosis genes while the expression of the Bcl2 gene is down-regulated in all studied cell lines, significantly. Also, the results of the MTT test indicated that the free niosome has no significant cytotoxic effects against the HFF cell line which represents the biocompatibility of the synthesized niosomes. In general, based on the results of this study, it can be concluded that niosomes-loaded SeNPs have significant anti-microbial, anti-biofilm, and anti-cancer effects, which can be used as a suitable drug delivery system.
Assuntos
Neoplasias da Mama , Nanopartículas , Selênio , Humanos , Feminino , Lipossomos , Selênio/química , AntibacterianosRESUMO
Konjac glucomannan (KGM) is a water-soluble polysaccharide derived from the Amorphophallus's tuber and, as herbal medicine has shown, can suppress tumor growth or improve health. However, there has been no investigation into the effects of KGM on breast tumor-bearing mice. Therefore, in two cohort experiments, we assessed the effect of glucomannan at daily doses of 2 and 4 mg for 28 days as a dietary supplement and also glucomannan in combination with tumor lysate vaccine as an adjuvant. Tumor volume was monitored twice weekly. In addition, TNF-α cytokines and granzyme B (Gr-B) release were measured with ELISA kits, and IL-2, IL-4, IL-17, and IFN-γ were used as an index for cytotoxic T lymphocyte activity. Moreover, TGF-ß and Foxp3 gene expression were assessed in a real-time PCR test. The results show that glucomannan as a dietary supplement increased the IFN-γ cytokine and Th1 responses to suppress tumor growth. Glucomannan as a dietary supplement at the 4 mg dose increased the IL-4 cytokine response compared to control groups. In addition, cell lysate immunization with 2 or 4 mg of glucomannan suppressed tumor growth. As an adjuvant, glucomannan at both doses showed 41.53% and 52.10% tumor suppression compared with the PBS group. Furthermore, the administration of glucomannan as a dietary supplement or adjuvant reduced regulatory T cell response through decreasing TGF-ß and Foxp3 gene expression in the tumor microenvironment. In conclusion, glucomannan as a dietary supplement or adjuvant enhanced the immune responses of tumor-bearing mice and decreased immune response suppression in the tumor milieu, making it a potentially excellent therapeutic agent for lowering breast tumor growth.
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As the most common cancer in women, efforts have been made to develop novel nanomedicine-based therapeutics for breast cancer. In the present study, the in silico curcumin (Cur) properties were investigated, and we found some important drawbacks of Cur. To enhance cancer therapeutics of Cur, three different nonionic surfactants (span 20, 60, and 80) were used to prepare various Cur-loaded niosomes (Nio-Cur). Then, fabricated Nio-Cur were decorated with folic acid (FA) and polyethylene glycol (PEG) for breast cancer suppression. For PEG-FA@Nio-Cur, the gene expression levels of Bax and p53 were higher compared to free drug and Nio-Cur. With PEG-FA-decorated Nio-Cur, levels of Bcl2 were lower than the free drug and Nio-Cur. When MCF7 and 4T1 cell uptake tests of PEG-FA@Nio-Cur and Nio-Cur were investigated, the results showed that the PEG-FA-modified niosomes exhibited the most preponderant endocytosis. In vitro experiments demonstrate that PEG-FA@Nio-Cur is a promising strategy for the delivery of Cur in breast cancer therapy. Breast cancer cells absorbed the prepared nanoformulations and exhibited sustained drug release characteristics.
Assuntos
Neoplasias da Mama , Curcumina , Nanopartículas , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Feminino , Ácido Fólico/metabolismo , Humanos , Lipossomos/uso terapêutico , Polietilenoglicóis/uso terapêuticoRESUMO
Hepatitis B virus (HBV) infection is limited through vaccination against HBsAg formulated in the Alum adjuvant. However, this alum-formulated vaccine fails to be preventive in some cases, also known as non-responders. Recent studies have shown the immunomodulatory effect of α-tocopherol in various models. Here, we developed a new formulation for HBsAg using α-tocopherol, followed by assessment of immune responses. Experimental BALB/c mice were immunized with a commercial alum-based vaccine or the one formulated in α-tocopherol at different doses. Mice were immunized subcutaneously with 5 µg of HBsAg with different formulations three times with 2-week intervals. Specific total IgG, IgG1, and IgG2a isotypes of antibodies were measured by ELISA. Immunologic cytokines, such as IFN-γ, IL-4, IL-2, and TNF-α, were also evaluated through commercial ELISA kits. Our results showed that the new α-tocopherol-formulated vaccine had the ability to reinforce specific total IgG responses. Moreover, α-tocopherol in the HBsAg vaccine increased IFN-γ, IL-2, and TNF-α cytokines at higher concentrations; however, the vaccine suppressed IL-4 cytokine release. At a lower concentration of α-tocopherol, the IL-4 cytokine response increased without a positive effect on IFN-γ and TNF-α cytokine response. It seems that α-tocopherol can change the immune responses against HBsAg; however, the type of response depends on the dose of α-tocopherol used in the vaccine formulation.
Assuntos
Citocinas , Vacinas contra Hepatite B , Interferon gama/imunologia , Adjuvantes Imunológicos , Animais , Citocinas/imunologia , Anticorpos Anti-Hepatite B , Vacinas contra Hepatite B/imunologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
In the present study, a magnetic niosomal nanocarrier for co-delivery of curcumin and letrozole into breast cancer cells has been designed. The magnetic NiCoFe2O4 core was coated by a thin layer of silica, followed by a niosomal structure, allowing us to load letrozole and curcumin into the silica layer and niosomal layer, respectively, and investigate their synergic effects on breast cancer cells. Furthermore, the nanocarriers demonstrated a pH-dependent release due to the niosomal structure at their outer layer, which is a promising behavior for cancer treatment. Additionally, cellular assays revealed that the nanocarriers had low cellular uptake in the case of non-tumorigenic cells (i.e., MCF-10A) and related high viability but high cellular uptake in cancer cell lines (i.e., MDA-MB-231 and SK-BR-3) and related low viability, which is evidenced in their high cytotoxicity against different breast cancer cell lines. The cytotoxicity of the letrozole/curcumin co-loaded nanocarrier is higher than that of the aqueous solutions of both drugs, indicating their enhanced cellular uptake in their encapsulated states. In particular, NiCoFe2O4@L-Silica-L@C-Niosome showed the highest cytotoxicity effects on MDA-MB-231 and SK-BR-3 breast cancer cells. The observed cytotoxicity was due to regulation of the expression levels of the studied genes in breast cancer cells, where downregulation was observed for the Bcl-2, MMP 2, MMP 9, cyclin D, and cyclin E genes while upregulation of the expression of the Bax, caspase-3, and caspase-9 genes was observed. The flow cytometry results also revealed that NiCoFe2O4@L-Silica-L@C-Niosome enhanced the apoptosis rate in both MDA-MB-231 and SK-BR-3 cells compared to the control samples. The findings of our research show the potential of designing magnetic niosomal formulations for simultaneous targeted delivery of both hydrophobic and hydrophilic drugs into cancer cells in order to enhance their synergic chemotherapeutic effects. These results could open new avenues into the future of nanomedicine and the development of theranostic agents.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Campos Magnéticos , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Feminino , Humanos , Letrozol/química , Letrozol/farmacocinética , Letrozol/farmacologia , Lipossomos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Proteínas de Neoplasias/metabolismoRESUMO
Cancer is one of the most common causes of mortality, and its various treatment methods can have many challenges for patients. As one of the most widely used cancer treatments, chemotherapy may result in diverse side effects. The lack of targeted drug delivery to tumor tissues can raise the possibility of damage to healthy tissues, with attendant dysfunction. In the present study, an optimum formulation of curcumin-loaded niosomes with a calcium alginate shell (AL-NioC) was developed and optimized by a three-level Box-Behnken design-in terms of dimension and drug loading efficiency. The niosomes were characterized by transmission electron microscopy, Fourier-transform infrared spectroscopy, and dynamic light scattering. The as-formulated niosomes showed excellent stability for up to 1 month at 4 °C. Additionally, the niosomal formulation demonstrated a pH-dependent release; a slow-release profile in physiological pH (7.4), and a more significant release rate at acidic conditions (pH = 3). Cytotoxicity studies showed high compatibility of AL-NioC toward normal MCF10A cells, while significant toxicity was observed in MDA-MB-231 and SKBR3 breast cancer cells. Gene expression studies of the cancer cells showed downregulation of Bcl2, cyclin D, and cyclin E genes, as well as upregulation of P53, Bax, caspase-3, and caspase-9 genes expression following the designed treatment. Flow cytometry studies confirmed a significant enhancement in the apoptosis rate in the presence of AL-NioC in both MDA-MB-231 and SKBR3 cells as compared to other samples. In general, the results of this study demonstrated that-thanks to its biocompatibility toward normal cells-the AL-NioC formulation can efficiently deliver hydrophobic drugs to target cancer cells while reducing side effects.
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Coronavirus disease 2019 (COVID-19) as a life-threatening disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is accounted as global public health concern. Treatment of COVID-19 is primarily supportive and the role of antiviral agents is yet to be established. However, there are no specific anti-COVID-19 drugs and vaccine until now. This review focuses on traditional medicine such as medicinal plant extracts as promising approaches against COVID-19. Chinese, Indian and Iranian traditional medicine, suggests some herbs for prevention, treatment and rehabilitation of the diseases including COVID-19. Although, inhibition of viral replication is considered as general mechanism of herbal extracts, however some studies demonstrated that traditional herbal extracts can interact with key viral proteins which are associated with virus virulence. Chinese, Indian and Iranian traditional medicine, suggests some herbs for prevention, treatment and rehabilitation of the diseases including COVID-19. However the beneficial effects of these traditional medicines and their clinical trials remained to be known. Herein, we reviewed the latest updates on traditional medicines proposed for treatment of COVID-19.
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Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Plantas Medicinais , Pneumonia Viral/tratamento farmacológico , COVID-19 , China , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Índia , Irã (Geográfico) , Pandemias , SARS-CoV-2 , Tratamento Farmacológico da COVID-19RESUMO
In this study, the antibacterial, anti-efflux, anti-biofilm, anti-slime (exopolysaccharide) production and urease inhibitory efficacies of green synthesized gold nanoparticles (AuNPs) coated Anthemis atropatana extract against multidrug- resistant (MDR) Klebsiella pneumoniae strains were evaluated. The green synthesized AuNPs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffractometer (XRD), particle size distribution, zeta potential and Fourier-transform infrared spectroscopy (FTIR). Then, antibacterial, anti-slime (exopolysaccharide) production, anti-biofilm and anti-efflux activities of AuNPs were investigated using micro-dilation, Congored agar, microtiter plate and MIC of ethidium bromide methods, respectively. Subsequently, the expression of mrkA, wzm and acrB genes was evaluated using quantitative Real-Time PCR (qRT-PCR). The synthesized AuNPs exhibited antibacterial activity against MDR strains of K. pneumoniae (minimum inhibitory concentration (MIC) of 6.25-50 µg/ml), as well as showed significant anti-slime (exopolysaccharide) production, anti-biofilm and anti-efflux activities against MDR strains. AuNPs showed significant inhibition against jack-bean urease and down-regulated the expression of mrkA, wzm and acrB genes. Moreover, the in vitro cytotoxic activity confirmed by MTT assay on the HEK-293 normal cell line showed negligible cytotoxicity. Thus, the present study suggests the potential use of AuNPs in the development of novel therapeutics for the prevention of biofilm-associated K. pneumoniae infections.
Assuntos
Anthemis/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Ouro/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Nanopartículas Metálicas , Extratos Vegetais/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ouro/química , Células HEK293 , Humanos , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Urease/metabolismoRESUMO
The aim of the present work was to investigate the antibacterial, antibiofilm, and antiquorum sensing activities of phytosynthesized silver nanoparticles (AgNPs) fabricated from Mespilus germanica extract against multidrug-resistant (MDR) Klebsiella pneumoniae strains. Fifty strains of K. pneumoniae were isolated from various clinical specimens. Biofilm-forming strains were identified using Congo red agar and polymerase chain reaction (PCR) techniques. Subsequently, the antibacterial activity of phytosynthesized AgNPs on MDR K. pneumoniae strains was investigated by broth microdilution assay and agar well-diffusion method. Finally (in the last step), the antibiofilm activity of phytosynthesized AgNPs was determined using microtiter plate assay and real-time PCR (RT-PCR) methods for the analysis of type 3 fimbriae (mrkA) and quorum-sensing system (luxS) gene expression. The results of this study showed that the phytosynthesized AgNPs had a spherical nanostructure with the mean size of 17.60 nm. The AgNPs exhibited dose-dependent antibacterial activity. The results of the microtiter plate and RT-PCR methods show that AgNPs inhibited the biofilm formation in MDR K. pneumoniae strains, and the expressions of mrkA and luxS genes were downregulated significantly in MDR strains after treatment with a subminimum inhibitory concentration of AgNPs. In conclusion, AgNPs effectively prevent the formation of biofilms and kill bacteria in established biofilms, which suggests that AgNPs might be a promising candidate for the prevention and treatment of biofilm-related infections caused by MDR K. pneumoniae strains.
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Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Nanopartículas Metálicas/química , Rosaceae/química , Prata/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Química Verde , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/fisiologia , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Percepção de Quorum/genética , Prata/químicaRESUMO
Silver nanoparticles (AgNPs) are at the forefront of the swiftly developing scope of nanotechnology. In the current study, we investigated the green synthesis of AgNPs using Artemisia scoporia as a reducing and capping agent. The biosynthesized AgNPs were characterized using ultraviolet-visible spectroscopy, X-ray diffraction, Fourier-Transform infrared spectroscopy, dispersive absorption spectroscopy, scanning electron microscopy, and transmission electron microscopy. The efficacy of the nanoparticle synthesis was assessed by comparing the antibiofilm activity with commercial AgNPs. The effect of sub-minimum inhibitory concentrations (MICs) of AgNPs on biofilm formation was determined by microtiter plate assay. The expression level of the icaA and icaR genes was assessed by real-time polymerase chain reaction assay. The structural and functional aspects of AgNPs were confirmed. The expression levels of icaA and icaR in the isolates exposed to sub-MIC of both commercial and biosynthetic AgNPs were lower and higher than in the control group, respectively. Our results also indicated that greater reduction and induction in icaA and icaR gene expression were noticed with the sub-MIC doses of biosynthetic AgNP versus commercial AgNP, respectively. This study suggested the application of AgNPs as a significant therapeutic and clinical option in the future and usage for fabricating medical implants. Nevertheless, further investigation is required for examining the pharmaceutical and medicinal properties of AgNPs.
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Artemisia/química , Biofilmes/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Farmacorresistência Bacteriana Múltipla , Química Verde , Humanos , Testes de Sensibilidade Microbiana , Nanomedicina , Extratos Vegetais/química , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/isolamento & purificaçãoRESUMO
Silver nanoparticles (AgNPs) were synthesized using Artemisia oliveriana extract, and their physicochemical characteristics were studied. The antioxidant and antimicrobial activities of the AgNPs, as well as their anticancer effects on the lung cancer cell line (A549), using 1,1-diphenyl-2-picrylhydrazyl (DPPH), MIC and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) techniques respectively demonstrated that the synthesized AgNPs mainly affected the gram-positive bacteria rather than the gram-negative bacteria, and exhibited significant cellular toxicity on the A549 cell line. Further, the cellular uptake of the AgNPs results indicated that the AgNPs accumulated within the cell. Moreover, their impact on the expression of apoptotic genes including Bax, Bcl-2, caspase-3 (CASP3), caspase-9 (CASP9) and miR-192 using real-time PCR demonstrated substantial increase in the expression of all mentioned genes (p<.001). Finally, the apoptotic effects of the AgNPs through DNA fragmentation test, flow cytometry and cell cycle analysis indicated the induction of apoptosis in the A549 cell line. The results revealed that the AgNPs synthesized using A. oliveriana extract have potential biological applications.
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Antineoplásicos , Artemisia/química , Ouro , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas Metálicas , Extratos Vegetais/química , Células A549 , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ouro/química , Ouro/farmacologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , MicroRNAs/biossíntese , Proteínas de Neoplasias/biossíntese , RNA Neoplásico/biossínteseRESUMO
Introduction: Linum album is a medicinal plant endemic in Iran that is very important pharmaceutically. The present study concerns the effect of different extracts of L. album on ZNF703 gene expression and apoptosis in human gastric carcinoma AGS cells. Method and material: Hydro alchoholic L. album extracts from various plant sources were produced by Maceration. AGS cells were treated with different concentrations (200, 400, 600, 800 and 1000 µg/ml) and the cytotoxicity potency was assessed after 24 h by MTT assay. Then, quantitative real time PCR was conducted for ZNF703 gene expression in AGS cells. Also, cell apoptosis/necrosis was assessed with the aid of Annexin V/PI staining and quantification by flow cytometry. Results: L. album extracts exerted dose-dependent toxicity in the AGS cell line. The mRNA levels of ZNF703 gene expression were significantly decreased with rhizome, fruit at fruiting, leaf and stem at anthesis (P<0.001), and leaf and stem at fruiting extracts as compared to the controls (P<0.01). Also, the number of apoptotic cells was increased from 2.70% (statistically significant; p<0.05) in untreated AGS cells to 44%, following treatment with the leaf and stem at anthesis example. Discussion: Our findings revealed that the L. album extracts can induce apoptosis and might modulate cytotoxicity by down regulating ZNF703 gene expression in AGS cells. Therefore, this extract could be a good candidate for inhibiting cancer cell growth, especially that of gastric cancer. In addition, ZNF703 may have potential as a therapeutic target.
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Adenocarcinoma/tratamento farmacológico , Apoptose/efeitos dos fármacos , Proteínas de Transporte/genética , Linho/química , Oncogenes/efeitos dos fármacos , Extratos Vegetais/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/genética , Anexina A5/genética , Antineoplásicos Fitogênicos/farmacologia , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Expressão Gênica/efeitos dos fármacos , Humanos , Oncogenes/genética , Plantas Medicinais/química , Neoplasias Gástricas/genéticaRESUMO
The focus of this study is on a rapid and cost-effective approach for the synthesis of silver nanoparticles (AgNPs) using Artemisia quttensis Podlech aerial parts extract and assessment of their antioxidant, antibacterial and anticancer activities. The prepared AgNPs were determined by ultraviolet-visible spectroscopy, X-ray diffraction, Fourier transform infra-red spectroscopy, transmission electron microscopy, scanning electron microscopy, energy-dispersive spectroscopy, and dynamic light scattering and zeta-potential analysis. The AgNPs and A. quttensis extract were evaluated for their antiradical scavenging activity by 2, 2-diphenyl, 1-picryl hydrazyl assay and anticancer activity against colon cancer (human colorectal adenocarcinoma cell line 29) compared with normal human embryonic kidney (HEK293) cells. Also, the prepared AgNPs were studied for its antibacterial activity. The AgNPs revealed a higher antioxidant activity compared with A. quttensis extract alone. The phyto-synthesised AgNPs and A. quttensis extract showed a dose-response cytotoxicity effect against HT29 and HEK293 cells. As evidenced by Annexin V/propidium iodide staining, the number of apoptotic HT29 cells was significantly enhanced, following treatment with AgNPs as compared with untreated cells. Besides, the antibacterial property of the AgNPs indicated a significant effect against the selected pathogenic bacteria. These present obtained results show the potential applications of phyto-synthesised AgNPs using A. quttensis aerial parts extract.
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Antibacterianos/administração & dosagem , Antifúngicos/administração & dosagem , Antineoplásicos/administração & dosagem , Artemisia/química , Sobrevivência Celular/efeitos dos fármacos , Nanopartículas Metálicas/administração & dosagem , Prata/administração & dosagem , Antibacterianos/síntese química , Antifúngicos/síntese química , Antineoplásicos/síntese química , Fenômenos Fisiológicos Bacterianos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Composição de Medicamentos/métodos , Fungos/efeitos dos fármacos , Células HEK293 , Células HT29 , Células HeLa , Humanos , Células MCF-7 , Teste de Materiais , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula , Fotoquímica/métodos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Prata/química , Resultado do TratamentoRESUMO
The present study aim to investigate the phytochemical composition, antibacterial, antioxidant and anticancer activities of the ethanolic extract from aerial parts of Artemisia quettensis Podlech. The aerial part of A. quettensis Podlech extract was used for Gas chromatography-mass spectrometry (GC-MS) analysis, antioxidant, antibacterial and anticancer activities. GC/MS analysis of extract from this plant showed 23 major components and the most dominant components were acetic acid, [4-(1-hydroxy-1-methylethyl) cyclohex-1-enyl] methyl ester (13.88%), trans-Phytol (10.06%) and 2,6-Dimethyl-2,6-octadiene-1,8-diol diacetate (6.8%). The extract had significant antibacterial and anticancer effects. The highest percentage of antioxidant activity was 78.46% at 2 mg/mL concentration of extract. Moreover, the highest antibacterial effects of extract were against to gram-positive bacteria and the IC50 cell cytotoxicity value on HT29 cell line in 24 h, 48 h and 72 h were 31.54, 6.08 and 2.96 mg/mL, respectively. From this study, A. quettensis Podlech could be considered as a promising source for novel drug compounds.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Artemisia/química , Extratos Vegetais/farmacologia , Antibacterianos/química , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Diterpenos/análise , Avaliação Pré-Clínica de Medicamentos/métodos , Etanol/química , Cromatografia Gasosa-Espectrometria de Massas , Bactérias Gram-Positivas/efeitos dos fármacos , Células HT29 , Humanos , Testes de Sensibilidade Microbiana , Componentes Aéreos da Planta/química , Extratos Vegetais/químicaRESUMO
The present study was to investigate the gas chromatography/mass spectrometry (GC/MS), in vitro antioxidant, antibacterial and anticancer activity of the ethanolic extract from aerial parts of Artemisia marschalliana Sprengel against human gastric carcinoma (AGS) and L929 cell lines. Phytochemical analysis of A. marschalliana Sprengel extract showed 22 major components and the most dominant compounds were trans-phytol (29.22%), α-Linolenic acid (13.47%) and n-Hexadecanoic acid (9.28%). In addition, the antioxidant and anticancer activity of A. marschalliana Sprengel extract were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods, respectively. Antibacterial activity against selected pathogenic bacteria was also determined. According to the present obtained results, it seems that this plant has potential uses for pharmaceutical industries and further studies of pharmaceutical importance were suggested to be performed on A. marschalliana Sprengel.