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1.
Pharm Dev Technol ; : 1-9, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34939892

RESUMO

Pistacia atlantica has an anti-cancer effect due to its essential oil which is the major constituent of P. atlantica. Unfortunately, this essential oil evaporates easily and makes it less effective. The current research, therefore, aimed to improve the anti-cancer effect of P. atlantica essential oil (PAEO) in solid lipid nanoparticles (SLN). The chemical components of PAEO were assessed by gas chromatography. PAEO-SLNs were prepared by the probe-ultrasonication method, and their particle size, polydispersity index and zeta potential were determined. Encapsulation Efficiency (EE%) and Loading Capacity (LC%) of formulations was also calculated. Transmission electron microscopy was employed to determine the morphology of optimal formulation (PAEO-SLN4). Furthermore, the anticancer effects of PAEO-SLN4 against MDA-MB-231 cells were evaluated by cellular assays. The results showed that the type of surfactant and loading of the essential oil had a significant effect on size distribution, zeta potential and the polydispersity index. The encapsulation efficiency (EE%) and loading capacity for PAEO-SLN4 were 97.3% and 9.6%, respectively. The cellular assay demonstrates that PAEO-SLN4 could lead MDA-MB-231 cells to apoptosis. The findings also revealed that PAEO-SLN4 can stimulate apoptosis in MDA-MB-231 cells more than the placebo and free PAEO thereby indicating PAEO-SLN4 to be beneficial in breast cancer treatment.

2.
Int J Nanomedicine ; 15: 4607-4623, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636621

RESUMO

Aim: The interaction of NPs with biological systems may reveal useful details about their pharmacodynamic, anticancer and antibacterial effects. Methods: Herein, the interaction of as-synthesized Co3O4 NPs with HSA was explored by different kinds of fluorescence and CD spectroscopic methods, as well as molecular docking studies. Also, the anticancer effect of Co3O4 NPs against leukemia K562 cells was investigated by MTT, LDH, caspase, real-time PCR, ROS, cell cycle, and apoptosis assays. Afterwards, the antibacterial effects of Co3O4 NPs against three pathogenic bacteria were disclosed by antibacterial assays. Results: Different characterization methods such as TEM, DLS, zeta potential and XRD studies proved that fabricated Co3O4 NPs by sol-gel method have a diameter of around 50 nm, hydrodynamic radius of 177 nm with a charge distribution of -33.04 mV and a well-defined crystalline phase. Intrinsic, extrinsic, and synchronous fluorescence as well as CD studies, respectively, showed that the HSA undergoes some fluorescence quenching, minor conformational changes, microenvironmental changes as well as no structural changes in the secondary structure, after interaction with Co3O4 NPs. Molecular docking results also verified that the spherical clusters with a dimension of 1.5 nm exhibit the most binding energy with HSA molecules. Anticancer assays demonstrated that Co3O4 NPs can selectively lead to the reduction of K562 cell viability through the cell membrane damage, activation of caspase-9, -8 and -3, elevation of Bax/Bcl-2 mRNA ratio, ROS production, cell cycle arrest, and apoptosis. Finally, antibacterial assays disclosed that Co3O4 NPs can stimulate a promising antibacterial effect against pathogenic bacteria. Conclusion: In general, these observations can provide useful information for the early stages of nanomaterial applications in therapeutic platforms.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Cobalto/química , Cobalto/farmacologia , Nanopartículas Metálicas/química , Óxidos/química , Óxidos/farmacologia , Albumina Sérica Humana/metabolismo , Antibacterianos/química , Antibacterianos/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobalto/metabolismo , Escherichia coli/efeitos dos fármacos , Humanos , Células K562 , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Óxidos/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Albumina Sérica Humana/química , Staphylococcus aureus/efeitos dos fármacos , Difração de Raios X
3.
Adv Pharm Bull ; 10(2): 323-328, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32373503

RESUMO

Purpose: Triple-negative breast cancer (TNBC) is specified by high vascularity and repetitious metastasis. Although several studies have indicated that angiogenesis has an important role in invasive breast cancer, a suitable model of TNBC that can show the exact onset of angiogenesis factors still needs to be developed. The purpose of this study is to determine the expression level of angiogenesis factors in different clinical stages of the 4T1 tumor as TNBC mouse model. Methods: Twenty mice were injected by the 4T1 cell line, and four mice selected as healthy controls. Following by tumor induction, the mice were randomly put into four groups, each contains four mice. Once the tumor volume reached to the early stage (<100 mm3), intermediate stage (100-300 mm3), advanced stage (300-500 mm3), and end stage (>500 mm3), they were removed by surgery. Then, the expression levels of Hif1α, VEGFR1, and VEGFR2 genes, as well as tumor markers of VEGF, bFGF and CD31, were evaluated by qPCR and immunohistochemistry (IHC) respectively. The statistical analysis was done by SPSS version 16. Results: TNBC tumors were confirmed and multi-foci metastasis in the lung were seen. The mRNA and protein expression levels of the angiogenesis factors increased in the early stage and as the tumor grew, their expression level enhanced dramatically. Conclusion: The 4T1 syngeneic mouse tumor may serve as an appropriate TNBC model for further investigation of the angiogenesis and therapies. Moreover, angiogenesis factors are induced before the advanced stage, and anti-angiogenesis therapy is necessary to be considered at the first line of treatment in TBNC.

4.
Int J Nanomedicine ; 14: 8433-8444, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749617

RESUMO

Aims: Different kinds of vitamins can be used as promising candidates to mitigate the structural changes of proteins and associated cytotoxicity stimulated by NPs. Therefore, the structural changes of α-syn molecules and their associated cytotoxicity in the presence of SWCNTs either alone or co-incubated with vitamin K1 were studied by spectroscopic, bioinformatical, and cellular assays. Methods: Intrinsic and ThT fluorescence, CD, and Congo red absorption spectroscopic approaches as well as TEM investigation, molecular docking, and molecular dynamics were used to explore the protective effect of vitamin K1 on the structural changes of α-syn induced by SWCNTs. The cytotoxicity of α-syn/SWCNTs co-incubated with vitamin K1 against SH-SY5Y cells was also carried out by MTT, LDH, and caspase-3 assays. Results: Fluorescence spectroscopy showed that vitamin K1 has a significant effect in reducing SWCNT-induced fluorescence quenching and aggregation of α- syn. CD, Congo red adsorption, and TEM investigations determined that co-incubation of α- syn with vitamin K1 inhibited the propensity of α-syn into the structural changes and amorphous aggregation in the presence of SWCNT. Docking studies determined the occupation of preferred docked site of SWCNT by vitamin K1 on α- syn conformation. A molecular dynamics study also showed that vitamin K1 reduced the structural changes of α- syn induced by SWCNT. Cellular data exhibited that the cytotoxicity of α- syn co-incubated with vitamin K1 in the presence of SWCNTs is less than the outcomes obtained in the absence of the vitamin K1. Conclusion: It may be concluded that vitamin K1 decreases the propensity of α- syn aggregation in the presence of SWCNTs and induction of cytotoxicity.


Assuntos
Nanotubos de Carbono/química , Vitamina K 1/farmacologia , alfa-Sinucleína/química , alfa-Sinucleína/metabolismo , Adsorção , Benzotiazóis/metabolismo , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Vermelho Congo , Humanos , L-Lactato Desidrogenase/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Nanotubos de Carbono/ultraestrutura , Espectrometria de Fluorescência
5.
Int J Biochem Cell Biol ; 116: 105615, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31539632

RESUMO

Although conventional therapeutic approaches have brought remarkable advantages for the treatment of breast cancer (BC), drug-resistance still remains as a leading cause of tumor recurrence in this malignancy. In the present study, we designed experiments to evaluate the therapeutic value of PI3K inhibition in combination with Arsenic trioxide (ATO) in MCF-7 cells. The results of our study manifested that BKM120 sensitized MCF-7 cells to the lower concentrations of ATO. The significant anti-cancer effect of PI3K inhibition became even more evident when we found that BKM120, either as a single agent or in combination with ATO, reduced clonogenic ability of anoikis-resistant stem-like MCF-7 cells. Our findings also showed that BKM120 augmented ATO-induced anti-proliferative effects through inducing G1 arrest and reducing the incorporation of BrdU into the synthesized DNA of drugs-treated cells, which was coupled with c-Myc-mediated suppression of hTERT expression. Moreover, we found that in the presence of PI3K inhibitor, ATO is able to more profoundly induce apoptosis in MCF-7 cells, as revealed by the increment in the percentage of haplodiploid sub-G1 cells and the externalization of phosphatidylserine. Real-time PCR analysis also revealed that probably down-regulation of survivin coupled with up-regulation of forkhead family transcription factors is responsible for the enhancive effect of drugs in this cell line. Conclusively, this study shed lights on the effect of PI3K inhibition in chemo-sensitivity of MCF-7 cells, disclosing that combination of BKM120 and ATO could be a promising therapeutic approach in BC.


Assuntos
Aminopiridinas/farmacologia , Antineoplásicos/farmacologia , Trióxido de Arsênio/farmacologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/genética , Anoikis/efeitos dos fármacos , Anoikis/genética , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Combinação de Medicamentos , Sinergismo Farmacológico , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Fatores de Transcrição Forkhead/agonistas , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Humanos , Células MCF-7 , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilserinas/metabolismo , Transdução de Sinais , Survivina/antagonistas & inibidores , Survivina/genética , Survivina/metabolismo , Telomerase/antagonistas & inibidores , Telomerase/genética , Telomerase/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
6.
Int J Nanomedicine ; 14: 243-256, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30643404

RESUMO

Background: Nanoparticles (NPs) have been emerging as potential players in modern medicine with clinical applications ranging from therapeutic purposes to antimicrobial agents. However, before applications in medical agents, some in vitro studies should be done to explore their biological responses. Aim: In this study, protein binding, anticancer and antibacterial activates of zero valent iron (ZVFe) were explored. Materials and methods: ZVFe nanoparticles were synthesized and fully characterized by X-ray diffraction, field-emission scanning electron microscope, and dynamic light scattering analyses. Afterward, the interaction of ZVFe NPs with human serum albumin (HSA) was examined using a range of techniques including intrinsic fluorescence, circular dichroism, and UV-visible spectroscopic methods. Molecular docking study was run to determine the kind of interaction between ZVFe NPs and HSA. The anticancer influence of ZVFe NPs on SH-SY5Y was examined by MTT and flow cytometry analysis, whereas human white blood cells were used as the control cell. Also, the antibacterial effect of ZVFe NPs was examined on Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922), and Staphylococcus aureus (ATCC 25923). Results: X-ray diffraction, transmission electron microscope, and dynamic light scattering analyses verified the synthesis of ZVFe NPs in a nanosized diameter. Fluorescence spectroscopy analysis showed that ZVFe NPs spontaneously formed a complex with HSA through hydrogen bonds and van der Waals interactions. Also, circular dichroism spectroscopy study revealed that ZVFe NPs did not change the secondary structure of HSA. Moreover, UV-visible data presented that melting temperature (Tm) of HSA in the absence and presence of ZVFe NPs was almost identical. Molecular dynamic study also showed that ZVFe NP came into contact with polar residues on the surface of HSA molecule. Cellular assays showed that ZVFe NPs can induce cell mortality in a dose-dependent manner against SH-SY5Y cells, whereas these NPs did not trigger significant cell mortality against normal white bloods in the concentration range studied (1-100 µg/mL). Antibacterial assays showed a noteworthy inhibition on both bacterial strains. Conclusion: In conclusion, it was revealed that ZVFe NPs did not induce a substantial influence on the structure of protein and cytotoxicity against normal cell, whereas they derived significant anticancer and antibacterial effects.


Assuntos
Antibacterianos/administração & dosagem , Antineoplásicos/administração & dosagem , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Ferro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Albumina Sérica Humana/metabolismo , Antibacterianos/química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Humanos , Ferro/química , Nanopartículas Metálicas/química , Simulação de Acoplamento Molecular , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Conformação Proteica , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Albumina Sérica Humana/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismo , Células Tumorais Cultivadas
7.
Int J Nanomedicine ; 13: 6871-6884, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30498348

RESUMO

Background: Implementations of nanoparticles have been receiving great interest in medicine and technology due to their unique characteristics. However, their toxic impacts on the biological system are not well explored. Aim: This study aims to investigate the influence of fabricated nano graphene oxide (NGO) sheets on the secondary and quaternary structural alterations of human hemoglobin (Hb) and cytotoxicity against lymphocyte cells. Materials and methods: Different spectroscopic methods, such as extrinsic and synchronous fluorescence spectroscopy and far circular dichroism (CD) spectroscopy, molecular docking investigation, cellular assays (trypan blue exclusion, cellular uptake, ROS, cell cycle, and apoptosis), and molecular assay (fold changes in anti/proapoptotic genes [B-cell lymphoma-2 {BCL2}/BAX] expression levels) were used in this study. Results: Transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and zeta potential investigations revealed the nano-sized nature of NGOs with good colloidal stability. Extrinsic fluorescence spectroscopy by using 8-anilinonaphthalene-1 -sulfonic acid and synchronous fluorescence spectroscopy showed that NGOs can unfold the quaternary structure of Hb in the vicinity of Tyr residues. The CD investigation demonstrated that the α-helicity of Hb experienced substantial alteration upon interaction with increasing concentrations of NGOs. The molecular docking study showed that NGOs interacted with polar residues of Hb. Cellular and molecular assays revealed that NGOs lead to ROS formation, cell cycle arrest, and apoptosis through the BAX and BCL2 pathway. Conclusion: These data reveal that NGOs can induce some protein structural changes and stimulate cytotoxicity against normal cell targets. Therefore, their applications in healthy systems should be limited.


Assuntos
Apoptose/efeitos dos fármacos , Grafite/química , Hemoglobinas/química , Linfócitos/patologia , Nanopartículas/toxicidade , Óxidos/química , Fenômenos Biofísicos , Células Cultivadas , Hemoglobinas/metabolismo , Humanos , Linfócitos/efeitos dos fármacos , Simulação de Acoplamento Molecular , Nanopartículas/química , Conformação Proteica
8.
Int J Biol Macromol ; 118(Pt B): 1963-1973, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30009913

RESUMO

Study on the side effects of the nanoparticles (NPs) can provide useful information regarding their biological and medical applications. Herein, the colloidal stability of the silicon dioxide NPs (SiO2 NPs) in the absence and presence of tau was investigated by TEM and DLS techniques. Afterwards, the thermodynamic parameters of interaction between SiO2 NPs and tau were determined by fluorescence spectroscopy and docking studies. Finally, the cytotoxic effects of SiO2 NPs on the viability of PC12 cells were investigated by MTT, AO/EB staining and flow cytometry assays. TEM, DLS, and zeta potential investigations revealed that tau can reduce the colloidal stability of SiO2 NPs. Fluorescence spectroscopy study indicated that SiO2 NPs bound to the tau with high affinity through hydrogen bonds and van der Waals interactions. Docking study also determined that Ser, Thr and Tyr residues provide a polar microenvironment for SiO2 NPs/tau interaction. Cellular studies demonstrated that SiO2 NPs can induce cell mortality through both apoptosis and necrosis mechanisms. Therefore, it may be concluded that the biological systems such as nervous system proteins can affect the colloidal stability of NPs and vice versa NPs in the biological systems can bind to proteins and cell membranes non-specifically and may induce toxicity.


Assuntos
Simulação de Acoplamento Molecular , Nanopartículas , Dióxido de Silício/metabolismo , Dióxido de Silício/toxicidade , Proteínas tau/química , Proteínas tau/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Coloides , Células PC12 , Conformação Proteica , Estabilidade Proteica , Ratos , Dióxido de Silício/química , Propriedades de Superfície , Termodinâmica
9.
Iran J Pharm Res ; 12(3): 495-501, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24250655

RESUMO

Ischemia-reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. Ischemia-reperfusion brain injury initiates an inflammatory response involving the expression of adhesion molecules and cytokines. Twenty-four male Wistar rats (250-300 g body wt) were used in this study. The animals were divided into four groups of 6 rats each: I: Control group that was subjected to ischemia-reperfusion, II: Ischemia-reperfusion group that was subjected to all surgical procedures, III: Drug group that received pentoxifylline (200, 400 and 600 mg/kg) 60 min before and after ischemia and IV: Vehicle group that received saline. Seventy two h after ischemia-reperfusion, the hippocampus was taken for studying the changes in bcl-2 gene expression. We used quantitative real-time PCR for the detection of bcl-2 gene expression in ischemia and drug groups and then compared them to normal samples. The results showed the gene dosage ratio of 0.66 and 1.5 for ischemia group and the drug groups, respectively. The results also showed the bcl-2 gene expression declined in ischemia group as compared to the drug group. Furthermore, we observed a significant difference in the bcl-2 gene expression between ischemia and drug groups. These findings are consistent with anti-apoptotic properties of bcl-2 gene. Furthermore this method provides a powerful tool for the investigators to study brain ischemia and respond to the treatment drugs with anti-apoptotic agents.

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