Leukemia-derived Exosomes Can Induce Responses Related to Tumorigenesis on Non-tumoral Astrocytes.

Cancer is the second cause of disability and death worldwide. Identifying communication between cancer cells and normal cells can shed light on the underlying metastatic mechanisms. Among different suspected mechanisms, exosomes derived from cancer cells have been introduced as a main key player in metastatic processes. To this point, we evaluated the effects of exosomes derived from the leukemia nalm6 cell line on astrocytes behavior, such as proliferation and inflammatory pathways. To assess astrocyte responses, data were obtained by MTT, Annexin/PI to indicate proliferation and apoptosis. Further analyses were performed by Real-time PCR and western blot to assess the expression of IL6, IL1ß, NFkß, TNFα, and aquaporin-4 (AQP4). Our results demonstrated that the proliferation of astrocytes was significantly increased when treated with exosomes derived from Nalm6 cells. We also found that the expression of IL6, IL1ß, NFkß, and TNFα were significantly increased at the mRNA level when exposed to exosomes derived from Nalm6 cells. Finally, the mRNA and protein levels of AQP4 were profoundly increased after being treated by exosomes derived from Nalm6 cells. To sum up, our data indicated that the secretion of cancer cells could induce responses related to tumorigenesis. However, further studies on this topic are warranted to clarify exosomes' role in metastasis.

Nanolipid-loaded Preyssler polyoxometalate: Synthesis, characterization and invitro inhibitory effects on HepG2 tumor cells.

Polyoxometalate-based drugs have been selected by some researchers as alternative antitumor substances with promising results in suppression of tumor growth because of low toxicity towards the human body and high activity. In this research, for the first time, nanolipid-loaded Preyssler polyoxometalate with diameters of 230-250 nm was synthesized and characterized by the Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Analysis (EDAX), Atomic Force Microscopy (AFM), and Infrared (IR) spectroscopy. The nanoliposomes were found to be nearly spherical, without any agglomeration with the Entrapment Efficiency of 53.8%. In -vitro antitumor activity of the synthesized nanoliposomes was investigated using the MTT method on HepG2 tumor cells. Our findings showed enhanced anticancer activity for the nanolipid-loaded Preyssler (NLP) compared to the Sorafenib as a commercially drug at 72 h. Selectivity of the synthesized NLP and Sorafenib for cancer cells versus primary HFF cells was obtained as 4.2 and 2.2, respectively. The IC50 value of the loaded nanoliposomes for cancer cells and normal cells was equal to 470 and 2000 µg/mL, respectively at 72 h, which was much better compared to that of the Sorafenib (7 and 16 µg/mL, respectively).

Evaluation of the Cytotoxic Effect of the Brittle Star (Ophiocoma Erinaceus) Dichloromethane Extract and Doxorubicin on EL4 Cell Line.

Leukemia is a blood disease that creates from inhibition of differentiation and increased proliferation rate. The nature has been known as a rich source of medically useful substances. High diversity of bioactive molecules, extracted from marine invertebrates, makes them as ideal candidates for cancer research. The study has been done to investigate cytotoxic effects of dichloromethane brittle star extract and doxorubicin on EL4 cancer cells. Blood cancer EL4 cells were cultured and treated at different concentrations of brittle star (Ophiocoma erinaceus) dichloromethane extract at 24, 48 and 72 h. Cell toxicity was studied using MTT assay. Cell morphology was examined using an invert microscope. Further, apoptosis was examined using Annexin V-FITC, propodium iodide, DAPI, and Acridine orange/propodium iodide staining. Eventually, the apoptosis pathways were analyzed using measurement of Caspase-3 and -9 activity. The statistical analysis was performed using SPSS, ANOVA software, and Tukey's test. P<0.05 was considered to be significant. MTT assay and morphological observations showed that dichloromethane extract can inhibit cell growth in a dose dependent. The results considered 32 µg/mL of the extract as IC50. Also, doxorubicin suppressed EL4 proliferation as IC50=32 µg/mL. All experiments related to apoptosis analysis confirmed that dichloromethane brittle star extract and doxorubicin have a cytotoxic effect on EL4 cells inIC50 concentration. The study showed that dichloromethane brittle star extract is as an adjunct to doxorubicin in treatment of leukemia cells.

An identified antioxidant peptide obtained from ostrich (Struthio camelus) egg white protein hydrolysate shows wound healing properties.

CONTEXT: Ostrich (Struthio camelus) egg possesses a high amount of food proteins and thus plays an important role in nutrition. OBJECTIVE: Ostrich egg white proteins were hydrolyzed with pepsin and pancreatin to examine its antioxidant properties and further characterized the most active peptide. MATERIALS AND METHODS: Ostrich egg white protein hydrolysate (OEWPH) was fractionized using reversed phase high-pressure liquid chromatography (HPLC). The antioxidant activity of OEWPH and its HPLC fraction were investigated based on their scavenging capacity1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,2'-azinobis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS), superoxide ([Formula: see text]), hydroxyl (OH(•-)) radicals, and Cu(+2) chelating. In a wound healing assay, paravertebral excision (1 cm diameter) was made on the skin and the percentage of wound closure was measured at defined intervals (0, 3, 7, and 14 d). RESULTS: A potent antioxidant peptide named DG-10 with the sequence DAESLSRLLG (MW: 1060.18 ± 0.5 Da) was identified from OEWPH. The peptide DG-10 showed DPPH (IC50 = 0.0085 mg/ml), ABTS(•+) (IC50 = 0.56 mg/ml), superoxide (IC50 = 0.36 mg/ml), and hydroxyl (IC50 = 0.4 mg/ml) radical scavenger and copper chelating activity (IC50 = 0.28 mg/ml). In vitro cultured HFLF-pI 5, the cell model, also revealed that DG-10 could protect HFLF-pI 5 cells against H2O2-treated necrosis. Ointment composed of DG-10 peptide exhibited wound-healing properties on adult rats (Wistar strain). The percentage of wound closure in peptide-treated group was 98% by day 14. DISCUSSION AND CONCLUSION: Our results suggested that DG-10 is a natural agent obtained from ostrich egg possessing considerable antioxidant and wound-healing properties.

The Synergic Effects of Crocus Sativus L. and Low Frequency Electromagnetic Field on VEGFR2 Gene Expression in Human Breast Cancer Cells.

BACKGROUND: Angiogenesis, which is required for embryonic development and many physiological events, plays crucial role in many pathological conditions such as tumor growth and metastasis. Recent studies indicate anticancer and antitumor properties of saffron against human cancers. Many processes are affected by Electromagnetic Field (EMF) and its effect on proliferation and gene expression were examined. In this experimental study, the synergic effects of saffron and EMF on VEGFR2 gene expression in MCF7 cells were investigated. METHODS: Saffron was extracted using freeze dryer. MCF7 cells were grown in RPMI 1640 medium supplemented with 10% FBS and incubated at 37°C with 5% CO2. After 24 hr cells were treated with saffron extract at concentrations of 100, 200, 400 and 800 µg/ml. Forty eight hr after treatment all flasks were exposed with EMF (50 Hz, 0.004 T). Then total RNA was extracted and cDNA was synthetized using specific primer. Synthetized products were analyzed by Real Time PCR to determine expression level of VEGFR2. Data were analyzed by SPSS (ANOVA & Tukey). RESULTS: Critical inhibitory effect on VEGFR2 gene expression was 20% at 400 µg/ml. Synergic use of EMF and saffron extract showed most reduction (38%) at 100 µg/ml. On the other hand synergic use of 200, 400 and 800 µg/ml saffron aqua extract and EMF decline noticeably the VEGFR2 level of gene expression to 29, 35 and 36%, respectively. EMF itself also reduced VEGFR2 up to 25% in comparison with control group which is remarkable at p < 0.001. CONCLUSION: Results indicate a decrease in the expression of vascular endothelial growth factor receptor in the treated samples with saffron extract compared to control. This reduction in VEGFR2 level induced by synergic treatment of saffron and EMF which reveals induction of inhibitory effects of saffron on angiogenesis and could be also considered as a promising chemotherapeutic agent in breast cancer treatment.