Preparation of the Myricetin-Loaded PEGylated Niosomes and Evaluation of their in†vitro Anti-Cancer Potentials.

Several edible plants contain flavonoids, including myricetin (Myr), which perform a wide range of biological activities. Myr has antitumor properties against various tumor cells. In this study Myr-loaded PEGylated niosomes (Myr-PN) were prepared and their anti-cancer activities were evaluated in vitro. Myr-PNs were prepared as a tool for drug delivery to the tumor site. Myr-PN was characterized in terms of size, zeta potential, and functional groups using dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (SEM). The Myr-PN size was 241 nm with a polydispersity index (PDI) of 0.20, and zeta potential -32.7±6.6 mV. Apoptotic properties of Myr-PN against normal and cancer cell lines were determined by flow cytometry and real-time quantitative PCR. Cancer cells showed higher cytotoxicity when treated with Myr-PN compared with normal cells, indicating that the synthesized nanoparticles pose no adverse effects. Apoptosis was induced in cells treated with 250 µg/mL of Myr-PN, in which 45.2 % of cells were arrested in subG1, suggesting that Myr-PN can induce apoptosis. In vitro, the synthesized Myr-PN demonstrated potent anticancer properties. Furthermore, more research should be conducted in vitro and in vivo to study the more details of Myr-PN anti-cancer effects.

Novel formulation of parthenolide-loaded liposome coated with chitosan and evaluation of its potential anticancer effects in vitro.

BACKGROUND: In this study the formulation of parthenolide (PN), an anticancer agent extracted from a natural product, into a liposome (PN-liposome), was examined. The surface of the PN-liposome was modified using chitosan (PN-chitosome). By using real-time quantitative PCR and flow cytometry, we examined the release of PN-chitosomes, cytotoxicity, and ability to induce apoptosis in vitro. METHODS AND RESULTS: According to the present study, PN-chitosomes had a size of 251 nm which is acceptable for efficient enhanced permeation and retention (EPR) performance. PN-chitosomes were confirmed to be spherical in shape and size through FESEM analysis. In terms of encapsulation efficiency, 94.5% was achieved. PN-chitosome possessed a zeta potential of 34.72 mV, which was suitable for its stability. According to the FTIR spectra of PN and PN-chitosome, PN was chemically stable due to the intermolecular interaction between the liposome and the drug. After 48 h, only 10% of the PN was released from the PN-chitosome in PBS (pH 7.4), and less than 20% was released after 144 h. CONCLUSION: In a dose-dependent manner, PN-chitosome exhibited anticancer properties that were more cytotoxic against cancer cells than normal cells. Moreover, the formulation activated both the apoptosis pathway and cytotoxic genes in real-time qPCR experiments. According to the cytotoxicity and activating apoptosis of the prepared modified particle, PN-chitosome may be helpful in the treatment of cancer.

The dose-dependent neuroprotective effect of norepinephrine in improving memory retrieval in an experimental model of multiple sclerosis, experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is considered an immune-mediated inflammatory disorder that causes cognitive impairments by damaging the hippocampal tissue. Conversely, norepinephrine (NEP) has anti-inflammatory and re-myelinating properties, which improve cognitive impairments. The aim of this study was to assess the neuroprotective effects of NEP on learning and memory disorders in an experimental animal model of MS. Two guide cannulas were bilaterally implanted in the rat hippocampal CA1 regions. After recovery, the animals received 3 µl of 0.01% ethidium bromide (EtB) in each of both hippocampal regions. After three days, the rats were randomly divided into 6 groups (8 rats/group), including control, sham 1, sham 2, and three groups of NEP 0.25, 0.5, and 1 mg/kg by intrahippocampal injection. Behavioral tests (e.g. shuttle box test and open-field test) were then performed. Finally, ROS, MDA, GSH, TNF-α, IL-6, and IL-1ß concentrations in the left CA1 area, as well as using western-blot analysis, p-p38, p-JNK, p-AKT, p-ERK1/2, p-NMDA, p-AMPA, p-CREB, and BDNF proteins in the right CA1 region evaluated. The EtB injection increased ROS, MDA, TNF-α, IL-6, and IL-1ß levels, as well as p-JNK and p-P38, except all other proteins, while decreasing GSH content, as well as step-through latency and locomotor activity in sham groups compared to the control group. Conversely, NEP (0.5 and 1 mg/kg, particularly at the dose of 1 mg/kg) counterbalanced all the alterations mentioned above in comparison to the sham groups. The EtB induced learning and memory impairment; however, NEP dose-dependently restored these impairments to normal levels.

A novel nanoformulation of parthenolide coated with polydopamine shows selective cytotoxicity and induces apoptosis in gastric cancer cells.

An anticancer agent derived from a natural product, parthenolide (PN), was studied to formulate PN into poly(lactic-co-glycolic acid) (PLGA). Polydopamine (PDA) was employed to modify the surface of PN-PLGA. Following characterization, the PN-PLGA-PDA was evaluated for its in vitro release, cytotoxicity, and ability to induce apoptosis using flow cytometry and real-time quantitative PCR. According to the present study, PN-PLGA-PDA had a size of 195.5 nm which is acceptable for efficient enhanced permeation and retention (EPR) performance. The SEM results confirmed the size and spherical shape of the nanoparticles. The percentage of encapsulation efficiency was 96.9%. The zeta potential of PN-PLGA-PDA was - 31.8 mV which was suitable for its stability. FTIR spectra of the PN-PLGA-PDA indicated the chemical stability of the PN due to intermolecular hydrogen bonds between polymer and drug. The release of PN from PN-PLGA-PDA in PBS (pH 7.4) was only 20% during the first 48 h and less than 40% during 144 h. PN-PLGA-PDA exhibited anticancer properties in a dose-dependent manner that was more cytotoxic against cancer cells than normal cells. Moreover, real-time qPCR results indicated that the formulation activated apoptosis genes to exert its cytotoxic effect and activate the NF-kB pathway. Based on our findings, PN-PLGA-PDA could serve as a potential treatment for cancer.

Verbascoside inhibits paraquate-induced pulmonary toxicity via modulating oxidative stress, inflammation, apoptosis and DNA damage in A549 cell.

Paraquat (PQ), one of the most frequently used herbicides, can cause serious health problems in an exposed individual. In the present study, we investigated the protective effect of verbascoside (VB), a phenylpropanoid glycoside from lemon verbena, against PQ-induced A549 cell injury with a particular focus on the possible molecular pathways involved. A549 cells were exposed to PQ (300 µM) and different concentrations of VB (12.5, 25, and 50 µM). Cell viability, ROS content, the level of antioxidant enzymes (SOD, CAT and GPx) and inflammatory markers (IL-6 and TNF-α), as well as 8-OHdG, were detected using MTT assay and an ELISA kit. Western blotting and qRT-PCR were performed to measure the levels of caspase3 and NF-κB mRNA and protein expression. Exposure of cells to PQ caused viability loss and ROS increase. PQ also increased the levels of IL-6, TNF-α and 8-OHdG and decreased the antioxidant enzymes content. PQ treatment resulted in cell death by increasing the gene and protein expression level of caspase 3 and NF-κB. Treatment with VB notably increased cell survival, antioxidant enzymes activity, which concomitantly attenuated ROS, NF-κB and inflammatory mediator production. VB also inhibited apoptosis expression markers. These results indicated that VB could protect A549 cells against PQ induced cell injury by attenuation of ROS and inflammatory marker production and modulation of antioxidant enzymes. VB efficiently suppressed increased NF-κB and caspase-3 activity and formation of 8-OHdG and ultimately improved cell viability. Therefore, VB may be useful in the development of a new therapy for PQ-induced pulmonary toxicity.

The Ferula Assa-foetida Essential Oil Nanoemulsion (FAEO-NE) as the Selective, Apoptotic, and Anti-Angiogenic Anticancer Compound in Human MCF-7 Breast Cancer Cells and Murine Mammary Tumor Models.

The Ferula assa-foetida (FA) is the healthy common-consumed anticancer beverage in Iranian folk medicine. In the current study, we aimed to produce a nanoemulsion-based drug delivery system containing FA essential oil (FAEO) and evaluate its antioxidant and anticancer activity on both MCF-7 cells and murine mammary cancer tissue. The FAEO-loaded nanoemulsion (FAEO-NE) was produced and characterized by DLS, TEM, FTIR, and Zeta potential analysis. Radical (ABTS and DPPH) scavenging activity, cytotoxic, apoptotic, and anti-angiogenic potentials of the FAEO-NE were studied by applying antioxidant (ABTS-DPPH), MTT, AO/PI cell staining, and Q-PCR analysis. Finally, its anti-tumor impact was evaluated on murine mammary tumor models. The FAEO-NE exhibited a meaningful antioxidant activity. Also, its significant cell-selective cytotoxic, apoptotic, and anti-angiogenic impacts on MCF-7 cancer cells indicated its anticancer potential. Moreover, the progressive destruction of the murine mammary glands cancer tissue confirmed their anticancer activity. Regarding the FAEO-NE cell-selective cytotoxic, apoptotic, and anti-angiogenic activity on MCF-7 breast cancer cells, it has the potential to be studied as a safe efficient anti-breast cancer agent.

Vitamin B12 and estradiol benzoate improve memory retrieval through activation of the hippocampal AKT, BDNF, and CREB proteins in a rat model of multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) causes extensive damage in the hippocampus. Vitamin B12 (vit B12) and estradiol benzoate (EB) have anti-inflammatory and re-myelination properties that make them proper in improvement of cognitive impairment. This study aimed to evaluate the effects of these compounds on learning and memory disturbances. MATERIALS AND METHODS: 77 adult male rats were implanted with stainless steel guide cannula bilaterally into the hippocampal area. The animals received 3 µl intrahippocampal EtB 0.01% and were randomly divided into eleven groups (7 rats/group). The groups included control, peanut oil (sham1), distilled water (sham 2), vit B12 (0.25, 0.5, 1 mg/kg), EB (25 and 50 mg/kg), vit B12 (0.25 mg/kg) plus EB (25 mg/kg), vit B12 (0.5 mg/kg) plus EB (25 mg/kg), and vit B12 (1 mg/kg) plus EB (50 mg/kg). The control group received intrahippocampal saline (as solvent). The locomotor activity and learning and memory functions were evaluated by open-field and shuttle-box tests, respectively. AKT, CREB, and BDNF levels were analyzed by Western blotting. RESULTS: This study has found significant deficit in passive avoidance learning, locomotor activity, as well as decrease in the levels of phosphorylated AKT, BDNF, and CREB in groups that received EtB. Vit B12 (1 mg/kg), EB (50 mg/kg), and their combination markedly improved these side effects. CONCLUSION: This study demonstrated that vit B12 and estradiol benzoate, especially in combination therapy, can be helpful in treatment of memory problems and MS-induced dysfunction through activation of the hippocampal AKT, BDNF, and CREB proteins.

Putative mechanism for cancer suppression by PLGA nanoparticles loaded with Peganum harmala smoke extract.

Synthesis and investigation of biological activity of Peganum harmala smoke-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Peganum harmala smoke-loaded PLGA nanoparticles (PHSE-PNP) were produced by double emulsion solvent evaporation method and characterised by scanning electron microscopy (SEM), dynamic light scattering (DLS), and ζ-potential. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) for toxicity evaluation, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assay for antioxidant power, chorioallantoic membrane (CAM), qPCR, and scratch assay for angiogenesis and mouse cancer model for antitumor effects of PHSE-PNP's were used. PHSE-PNP with a size of 216.33 nm, polydispersity index (PDI): 0.22 and ζ-potential: -25.41 mV inhibited A2780, PC3, A549, HepG2, Mda-mb-231, HT-29 as cancer cells and HUVEC as an normal cells with half-maximal inhibitory concentration (IC50) at about 208.62, 479.05, 1092.6, 1103.9, 1299.21, 3467.5, and <4000 µg/ml, respectively. Also PHSE-PNP inhibited ABTS (IC50: 0.720 mg/ml), DPPH (IC50: 1.36 mg/ml) free radicals and decreased the size of murine tumours (88.3% in 11 days) and suppressed angiogenesis in the CAM and scratch assays. PHSE-PNP can be considered as a potential chemopreventive agent in cancer therapy.

The Anti-Breast Cancer Effects of Green-Synthesized Zinc Oxide Nanoparticles Using Carob Extracts.

BACKGROUND: The use of nanoparticles synthesized by the green method to treat cancer is fairly recent. The aim of this study was to evaluate cytotoxicity, apoptotic and anti-angiogenic effects and the expression of involved genes, of Zinc Oxide Nanoparticles (ZnO-NPs) synthesized with Carob extracts on different human breast cancer cell lines. METHODS: ZnO-NPs were synthesized using the extracts of Carob and characterized with various analytical techniques. The MCF-7 and MDA-MB231 cells were treated at different times and concentrations of ZnO-NPs. The cytotoxicity, apoptosis, and anti-angiogenic effects were examined using a series of cellular assays. Expression of apoptotic genes (Bax and Bcl2) and anti-angiogenic genes, Vascular Endothelial Growth Factor (VEGF) and its Receptor (VEGF-R) in cancer cells treated with ZnO-NPs were examined with Reverse Transcriptionquantitative Polymerase Chain Reaction (RT-qPCR). The anti-oxidant activities of ZnO-NPs were evaluated by ABTS and DPPH assay. RESULTS: Exposure of cells to ZnO-NPs resulted in a dose-dependent loss of cell viability. The IC50 values at 24, 48, and 72 hours were 125, 62.5, and 31.2µg/ml, respectively (p<0.001). ZnO-NPs treated cells showed, in fluorescent microscopy, that ZnO-NPs are able to upregulate apoptosis and RT-qPCR revealed the upregulation of Bax (p<0.001) and downregulation of Bcl-2 (p<0.05). ZnO-NPs increased VEGF gene expression while decreasing VEGF-R (p<0.001). The anti-oxidant effects of ZnO-NPs were higher than the control group and were dose-dependent (p<0.001). CONCLUSION: ZnO-NPs synthetized using Carob extract have the ability to eliminate breast cancer cells and inhibit angiogenesis, therefore, they could be used as an anticancer agent.

Bufo viridis secretions improve anxiety and depression-like behavior following intracerebroventricular injection of amyloid ß.

BACKGROUND AND PURPOSE: Venenum Bufonis is a Chinese traditional medicine produced from the glandular secretions of toads that contain biogenic amines, which have anti-inflammatory properties. The present study aimed to examine the effect of Bufo viridis secretions (BVS) on anxiety and depression-like behavior and hippocampal senile plaques volume in an animal model of Alzheimer's disease (AD). EXPERIMENTAL APPROACH: Thirty-eight male Wistar rats were used. AD was induced by amyloid-beta (Aß1-42) (10 µg/2 µL, intracerebroventricular injection, icv) and then BVS at 20, 40, and 80 mg/kg were injected intraperitoneally (ip) in six equal intervals over 21 days. Anxiety and depression-like behavior were assessed using behavioral tests including open field test (OFT), elevated plus maze (EPM), and forced swimming test (FST) 21 days after the surgery. The volume of senile plaques was assessed based on the Cavalieri principle. FINDINGS/RESULTS: Results of the OFT showed that the central crossing number and the time in the AD group were significantly decreased compared to the sham group (P < 0.01 and P < 0.001, respectively). Also, the values of these two parameters significantly increased in the AD + BVS80 group than the AD group (P < 0.05 and P < 0.001, respectively). The time spent in the closed arm in the EPM dramatically increased in the AD group compared to the sham group (P < 0.05) and significantly decreased in the AD + BVS80 group compared to the AD group (P < 0.05). Results of the FST indicated that immobility time had a reduction in the AD + BVS20 (P < 0.01), AD + BVS40, and AD + BVS80 groups compared to the AD group (P < 0.001). The volume of senile plaques in the hippocampus showed a reduction in the treatment groups in comparison with the AD group (P < 0.001 for all). CONCLUSION AND IMPLICATIONS: Results revealed that BVS injection could improve symptoms of anxiety and depression and decrease senile plaques in the hippocampus in an animal model of AD.

Improvement of Tracheal Responsiveness and Th1/Th2 Balance in a Rat Model of Asthma, Treated with Portulaca Oleracea.

CONTEXT: A large proportion of asthmatic patients use complementary and alternative medicine (CAM) for the treatment of their disease. Various pharmacological effects, including anti-inflammatory properties, have been described for Portulaca oleracea (P. oleracea). OBJECTIVE: The study intended to evaluate the effects of an extract of P. oleracea on interleukin 4 (IL-4) and interferon-gamma (INF-γ) and on the INF-γ /IL4 ratio, as an index for the balance of T helper 1 and 2 (Th1/Th2) cells, in bronchoalveolar lavage fluid (BALF) as well as on tracheal responsiveness (TR) in a rat model of asthma. DESIGN: The research team performed an animal study. ANIMALS: Forty-eight male Wistar rats, each weighing 220 ± 50 g, were included in the study. INTERVENTION: The rats were randomly divided into 6 groups: (1) a control group that was not induced with asthma and that received no treatments (C group), (2) a group induced with asthma that received no treatments (A group), (3) an intervention group induced with asthma and treated with one mg/ml of P. oleracea extract (PO 1 group), (4) an intervention group induced with asthma and treated with 2 mg/ml of P. oleracea extract (PO 2 group), (5) an intervention group induced with asthma and treated with 4 mg/ml of P. oleracea extract (PO 4 group), and (6) a positive control group induced with asthma and treated with 1.25 µg/ml dexamethasone (D group). The asthma was induced using ovalbumin (OVA). OUTCOME MEASURES: Tracheal responsiveness and the BALF levels of IL-4 and INF-γ and the INF-γ/IL4 ratio were measured. RESULTS: Tracheal responsiveness to methacholine in the A and PO 1 groups and to OVA in the A, PO 1, and PO 2 groups as well as the BALF levels of IL-4 in the A, D, PO 1, PO 2, and PO 4 groups were significantly higher than that of the C group. The BALF level of INF-γ and the INF-γ/IL4 ratio were significantly lower in the A, D, PO 1, PO 2, and PO 4 groups than in the C group. Only treatment with the 2 higher concentrations of the extract caused a concentration-dependent increase in the INF-γ/IL4 ratio (P < .001). The effects of the 2 higher concentrations of the extract on INF-γ and IL-4 and on the INF-γ/IL4 ratio were significantly greater than those of the dexamethasone treatment (P < .001). CONCLUSIONS: These results showed an immunomodulatory effect for the extract of P. oleracea with regard to an increased INF-γ/IL4 ratio, as an index of Th1/Th2, as well as a preventive effect on tracheal responsiveness, which was more specific than the effects of dexamethasone on the Th1/Th2 balance.

Mn(II) complex of a vitamin B6 Schiff base as an exclusive apoptosis inducer in human MCF7 and HepG2 cancer cells: Synthesis, characterization, and biological studies.

Herein, a Mn(II) complex of the N,N'-dipyridoxyl(1,4-butanediamine) (═H2 L) Schiff base has been newly synthesized. The synthesized complex was characterized by several experimental methods. In addition, the density functional theory approaches were used for theoretical identification of the complex. A good agreement between the computed and experimental infrared frequencies demonstrates validity of the optimized geometry for the synthesized complex. In a N2 O2 manner, two azomethine nitrogens and two phenolate oxygens of the L2- ligand are coordinated to the Mn2+ metal ion. The biological studies indicate an efficient apoptotic and antioxidant activities of the synthesized [MnL(CH3 OH)2 ] complex on both of the HepG2 and MCF7 cancer cells. Since it has been suggested that the complex is an exclusive potent antitumor for treatment of the human breast and liver cancers.

Anticancer Activities of Cu(II) Complex-Schiff Base and Low-Frequency Electromagnetic Fields and the Interaction Between Cu(II) Complex-Schiff Base with Bovine Serum Albumin by Spectroscopy.

Cancer is the consequence of abnormal cell proliferation, which leads to the formation of abnormal mass. In this study, we aimed to determine the anticancer properties of Cu(II)-Schiff base complex and low-frequency electromagnetic field, and the interaction between BSA and Cu(II) complex. Firstly, Schiff base of the Cu(II) complex in the N,N'-dipyridoxyl(1,2 diaminobenzene) was originally synthesized. Following, the breast cancer was transplanted with the TUBO cells in vivo. Then, treatment of the cancerous mice was done by low-frequency electromagnetic field and the Cu(II)-Schiff base complex. In this project, antiproliferative activity on breast cancer cells was tested by TUBO cells using MTT assay and apoptosis properties were studied by flow cytometry. The interaction between the Cu(II)-Schiff base complex and bovine serum albumin (BSA) was checked by fluorescence and UV-vis absorbance spectroscopy. Tumor tissue investigation demonstrated that the low-frequency electromagnetic field and Cu(II)-Schiff base complex induce apoptosis and inhibit tumor growth. MTT results unveiled a cytotoxic impact on breast cancer cells. Flow cytometry analysis demonstrates that the anticancer effect of Cu(II)-Schiff base complex on breast cancer cells (MCF7) was associated with the cell cycle arrest. The results of fluorescence spectra and UV-vis absorption spectra showed that the conformation of bovine serum albumin has been changed in the presence of Cu(II)-Schiff base complex. Cu(II)-Schiff base complex and low-frequency electromagnetic field have anticancer properties. The spectroscopy method indicates the binding between Cu(II)-Schiff base complex and BSA.

Galbanic acid: Induced antiproliferation in estrogen receptor-negative breast cancer cells and enhanced cellular redox state in the human dermal fibroblasts.

INTRODUCTION: Galbanic acid (GA) is a natural bioactive compound abundantly distributed in Ferula species (Apiaceae), with a wide range of biological functions. METHODS: The present study investigated the anticancer properties of GA in human breast carcinoma MCF-7 and MDA-MB-231 cell lines using MTT (3,4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) assay. Further, the antioxidant activity of GA was determined in vitro. The plausible mechanisms of action of GA were further investigated using flow cytometry and gene expression analysis. RESULTS: Our study indicated that treatment with GA resulted in inhibition of proliferation and induction of apoptosis in MDA-MB-231 cells. The obtained results indicated that GA has strong cytotoxicity on MDA-MB-231 cells (IC50 = 48.75 µg/mL) compare to MCF-7 (IC50 = 56.65 µg/mL) and decrease cancer cell viability in the dose- and time-dependent manner. Meanwhile, microscopic examination and flow cytometry analysis confirmed the apoptosis cell death upon treatment with GA. The gene expression analysis revealed that GA could induce apoptosis-mediated proliferation inhibition in MDA-MB-231 cells through upregulation of bax and caspase-3 and downregulation of bcl2 genes. Besides, the GA exhibited free radical-scavenging activity and enhanced the cellular redox state in human dermal fibroblasts. The elevation of cellular redox status was confirmed by upregulating superoxide dismutase, catalase, and glutathione peroxidase genes. CONCLUSION: The results obtained in this study indicated that GA could be considered as a promising anticancer agent in breast cancer therapy and a bioactive antioxidant compound to be used in pharmaceutical and cosmetic industries.

Green synthesized-zinc oxide nanoparticles, the strong apoptosis inducer as an exclusive antitumor agent in murine breast tumor model and human breast cancer cell lines (MCF7).

PURPOSE: In the present study, we aimed to synthesize and investigate the impact of zinc oxide nanoparticle (ZnONPs) on both human and murine breast cancer cell lines and define their untoxic concentrations (IC50 ) to clarify their apoptotic properties and introduce them as the anticancer agents. MATERIALS AND METHODS: The in vitro study was initiated by ZnONPs green synthesizing process applying the Cucumis melo inodorus rough shell extract, and verified by the transmission electron microscope, scanning electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction analysis. In following, the human (Michigan Cancer Foundation-7 [MCF7]) and murine (TUBO) breast cancer cell lines were cultured for taking the time and dose-dependent treatment planes by ZnONPs. Also, MCF7 cell cultures were treated by three different doses of ZnoNPs (8, 4, and 2 µg/mL) separately and prepared for genes expression (Cas-3 and Cas-8) analysis using real-time quantitative PCR method. The in vivo initiated by providing the 39 murine breast cancer models, then they were injected intraperitoneally with different doses of ZnONPs (75, 50, and 25 mg/kg) treatments. Then their collected biopsies were stained by hematoxylin and eosin to evaluate their breast cancer tissue morphology and compare with Tamoxifen anticancer properties. RESULTS: The in vitro study results demonstrate a significant correlation among the expression of Cas-3 and Cas-8 genes with increasing ZnONPs concentrations. The results of 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assays for the treated cancer cell lines (MCF7 and TUBO) detected a significant negative correlation among the ZnONPs concentrations and the viability of the cells. CONCLUSION: Unlike the majority of resent studies, we found the ZnONPs as a powerful apoptosis inducer in the human cell line (MCF7) and murine (TUBO cell line and cancer model).

Green synthesis of silver nanoparticles using Rubia tinctorum extract and evaluation the anti-cancer properties in vitro.

Cancer is one of the leading causes of human death. Nanotechnology could offer new and optimised anticancer agents in order to fight cancer. It was shown that metal nanoparticles, in particular silver nanoparticles (AgNPs) were effective in cancer therapy. In this study, AgNPs were synthesised using Rubia tinctorum L. extract (Ru-AgNPs). Then, cytotoxicity effects of the Ru-AgNPs against MDA-MB-231 carcinoma cell line and human dermal fibroblast as normal cell line were performed. Furthermore, anti-apoptotic effects of Ru-AgNPs on these cancer and normal cell lines were compared using acridine orange/propidium iodide staining, flow cytometry analysis and real-time qPCR in apoptosis gene markers. Results of UV-vis spectroscopy showed that Ru-AgNPs have a peak at 430 nm, which indicated synthesis of AgNPs. Ru-AgNPs had spherical shape and average size of 12 nm. Ru-AgNPs have cytotoxicity on MDA-MB-231 cells and decrease cancerous cell viability (IC50 = 4 µg/ml/48 h). Ru-AgNPs could induce apoptosis in MDA-MB-231 cells through upregulation of Bax and downregulation of Bcl-2 gene expression. The results opened up new avenues to develop Rubia based metal complexes as an anticancer agent.

Treatment of the breast cancer by using low frequency electromagnetic fields and Mn(II) complex of a Schiff base derived from the pyridoxal.

The breast cancer is the most common type of cancer in women. In this project, the breast cancer was transplanted in vivo with the TUBO cells. Then, the cancerous mice were treated by radiation of low frequency electromagnetic fields and injection of the Mn(II) complex of the N,N'-dipyridoxyl(1,2-diaminobenzene) Schiff base. Three different concentrations of the Mn(II) complex were used. Cytotoxicity and morphological alterations caused by the Mn(II) complex in the TUBO breast cancer cell line have been evaluated. Apoptotic properties of the Mn(II) complex was studied using the flow cytometry. The Mn(II) complex has a cytotoxic effect on cancer cells. Also, both of the Mn(II) complex and low frequency electromagnetic field induced apoptosis, which was confirmed by flow cytometry. Both of them result in considerable changes in the treated tissues such as decrease of the tumor mass, induction of apoptosis and decrease in number of the blood vessels.

The preventive effects of natural adjuvants, G2 and G2F on tracheal responsiveness and serum IL-4 and IFN-γ (th1/th2 balance) in sensitized guinea pigs.

OBJECTIVE: The effects of natural adjuvants on lung inflammation and tracheal responsiveness were examined in sensitized guinea pigs. METHODS: The responses of guinea pig tracheal chains and the serum levels of interleukin-4 and interferon-gamma were examined in control pigs and three other groups of guinea pigs: the sensitized group and two other sensitized groups treated with either adjuvant G2 or adjuvant G2F (n=7 for each group). Sensitization of the animals was achieved by injection and inhalation of ovalbumin. RESULTS: The results showed that sensitized animals had increased tracheal responsiveness and increased serum levels of interleukin-4 and interferon-gamma compared to controls (p<0.05 to p<0.001). Treatments with either G2 or G2F prevented the increase in tracheal responsiveness and serum interleukin-4 (p<0.01 to p<0.001). However, the serum levels of interferon-gamma and the interleukin-4-to-interferon-gamma ratio was increased in the treated groups (p<0.001 for all cases). CONCLUSIONS: These results indicate important preventive effects of two natural adjuvants, particularly G2, on the changes in tracheal responsiveness, serum cytokines and the interleukin-4-to-interferon-gamma ratio (T helper 1/T helper 2 balance) in sensitized guinea pigs.

The preventive effects of natural adjuvants, G2 and G2F on tracheal responsiveness and serum IL-4 and IFN-? (th1/th2 balance) in sensitized guinea pigs

OBJECTIVE: The effects of natural adjuvants on lung inflammation and tracheal responsiveness were examined in sensitized guinea pigs. METHODS: The responses of guinea pig tracheal chains and the serum levels of interleukin-4 and interferon-gamma were examined in control pigs and three other groups of guinea pigs: the sensitized group and two other sensitized groups treated with either adjuvant G2 or adjuvant G2F (n = 7 for each group). Sensitization of the animals was achieved by injection and inhalation of ovalbumin. RESULTS: The results showed that sensitized animals had increased tracheal responsiveness and increased serum levels of interleukin-4 and interferon-gamma compared to controls (p<0.05 to p<0.001). Treatments with either G2 or G2F prevented the increase in tracheal responsiveness and serum interleukin-4 (p<0.01 to p<0.001). However, the serum levels of interferon-gamma and the interleukin-4-to-interferon-gamma ratio was increased in the treated groups (p<0.001 for all cases). CONCLUSIONS: These results indicate important preventive effects of two natural adjuvants, particularly G2, on the changes in tracheal responsiveness, serum cytokines and the interleukin-4-to-interferon-gamma ratio (T helper 1/T helper 2 balance) in sensitized guinea pigs. .

The effect of natural adjuvants on pathological changes in sensitized Guinea pig lungs.

BACKGROUND: Anti-inflammatory effect of natural adjuvants has been reported. Lung inflammation is the most characterized pathological feature in asthma. OBJECTIVES: The effects of three natural adjuvants (PC, G2, and G2F registered as a patent in the Iranian Patent Office) on sensitized guinea pigs lungs were examined in the present study. MATERIALS AND METHODS: LUNG PATHOLOGICAL CHANGES WERE EXAMINED IN CONTROL AND FIVE GROUPS OF RANDOMLY DIVIDED GUINEA PIGS INCLUDING: sensitized animals (S, receiving normal saline, 0.5 ml i.p.); sensitized animals treated with adjuvant PC; G2F (0.1 ml i.p. for both cases); G2 (0.4 ml i.p.); and PC + G2 (receiving both PC and G) adjuvants (twice a week for 4 weeks for all groups). Sensitization of animals was done by injection and inhalation of ovalbumin (OA). RESULTS: All pathological changes in S group including the eosinophil infiltration (scoring 3.28 ± 0.28), lymphocyte infiltration (2.82 ± 0.26), local epithelial necrosis (2.71 ± 0.47) and mucosal plug (2.75 ± 0.37) were significantly higher than control group (0.64 ± 0.18, 1.36 ± 0.24, 0.36 ± 0.18 and 0.28 ± 0.18 for eosinophil infiltration, lymphocyte infiltration, epithelial necrosis and mucosal plug respectively, P < 0.001 for all cases). Treatment with all adjuvants improved all pathological changes significantly (P < 0.05 to P < 0.001). CONCLUSIONS: These results indicate preventive effects of all natural adjuvants (especially G2) on pathological changes of the lung in sensitized guinea pigs.