BackgroundBreast cancer is the most common type of cancer among females. Hypoxia mediates cancer hallmarks and results from reduced oxygen level due to irregularities in tumor vascularization or when the tumor size prevents oxygen diffusion and triggers angiogenesis to compensate for low oxygen. Cancer stem cells (CSCs) are a rare subpopulation, able to self-renew and to give rise to tumor-initiating cells. It is proposed that CSCs’ secretions help to recruit endothelial cells via angiogenic factors to establish tumor vascularization. In the tumor microenvironment, the effect of hypoxia on CSCs and the impact of their secretions on triggering angiogenesis and tumor vascularization remain questionable. In this study, three-dimensional (3D) CSCs derived from MCF-7 were directly exposed to repetitive long-term cycles of hypoxia to assess its effect on CSCs and then to evaluate the role of the hypoxic CSCs’ (CSCsHYP) secretions in angiogenesis using (HUVECs) as a model for tumor neovascularization response.MethodsCSCs derived from MCF-7 cell-line were expanded under repetitive, strictly optimized, long-term/continuous and intermittent hypoxic shots for almost four months to assess hypoxic effect on CSCs, sorted based on CD44+/CD24− biomarkers. Hypoxic phenotype of CSCsHYP was evaluated by assessing the acquired chemoresistance using MTT assay and elevated stemness properties were assessed by flow cytometry. To evaluate the effect of the secretions from CSCsHYP on angiogenesis, HUVECs were exposed to CSCsHYP conditioned-medium (CdM)—in which CSCs had been previously grown—to mimic the tumor microenvironment and to assess the effect of the secretions from CSCsHYP on the HUVECs’ capability of tube formation, migration and wound healing. Additionally, co-culture of CSCsHYP with HUVECs was performed.ResultsCSCsHYP acquired higher chemoresistance, increased stemness properties and obtained greater propagation, migration, and wound healing capacities, when compared to CSCs in normoxic condition (CSCsNOR). HUVECs’ tube formation and migration abilities were mediated by hypoxic (CSCs) conditioned media (CdM).DiscussionThis study demonstrates that chemoresistant and migrational properties of CSCs are enhanced under hypoxia to a certain extent. The microenvironment of CSCsHYP contributes to tumor angiogenesis and migration. Hypoxia is a key player in tumor angiogenesis mediated by CSCs.

Background: Hypoxic condition induces molecular alterations which affect the survival rate and chemo-resistant phenotype of cancer cells. Objective: The aim of this study is to investigate the influence of intermittent hypoxic conditions on the expression of glucose metabolism genes in breast cancer MCF7 cell line. Methods: The gene expression was analyzed using a polymerase chain reaction-array method. In addition, the cell resistance, survival and migration rates were examined to assure the hypoxic influence on the cells. Results: 30 hypoxic episodes induced the Warburg effect through significant (p-value < 0.05) upregulation of the expression of PCK2, PHKG1, ALDOC, G6PC, GYS2, ALDOB, HK3, PKLR, PGK2, PDK2, ACO1 and H6PD genes that are involved in glycolysis, were obtained. Furthermore, the expression of the major gluconeogenesis enzyme genes was significantly (ANOVA, p-value < 0.05) downregulated. These molecular alterations were associated with increased MCF7 cell division and migration rate. However, molecular and phenotypic changes induced after 30 episodes were normalized in MCF7 cells exposed to 60 hypoxic episodes. Conclusion: It is concluded, from this study, that 30 intermitted hypoxic episodes increased the survival rate of MCF7 breast cancer cells and induced the Warburg effect through upregulation of the expression of genes involved in the glycolysis pathway. These results may increase our understanding of the molecular alterations of breast cancer cells under hypoxic conditions.

Microgravity affects plant growth and content. A three-dimensional clinostat was used at 4 rotations/min to rotate the seeds of Triticum aestivum cultivar (Ammon) in three dimensions for 7 days, following which the antioxidant activities of ethanolic extracts were evaluated using both nitric oxide-and hydrogen peroxide-scavenging activities. The antidiabetic activities of ethanolic extracts were evaluated by measuring the concentration of plasma glucose, insulin, C peptide, and glycated hemoglobin (HbA1c); determining the number of β cells in the pancreatic islets; and performing the glucose tolerance test. Furthermore, the effects of the ethanolic extracts on the lipid profile and liver function were estimated. After rats were sacrificed, their pancreases were isolated and used for histopathological processing. The results indicated that the antioxidant potential and antioxidant metabolite content were significantly increased under microgravity conditions in comparison to those under normal gravity conditions. Rats treated with an extract of wheatgrass (T. aestivum) germinated over a period of 6-10 days under microgravity (WGM) showed a significant reduction in the levels of serum glucose, HbA1C, urea, creatinine, aspartate aminotransferase and alanine aminotransferase, and insulin resistance compared to rats treated with an extract of wheatgrass germinated under gravity. Additionally, the total cholesterol and low-density lipoprotein cholesterol levels were significantly decreased. In contrast, highdensity lipoprotein cholesterol, C-peptide, and insulin levels rose significantly after treatment with T. aestivum germinated under microgravity. WGM is a promising potential diabetic treatment without side effects with a low manufacturing cost.

Background: Increasing antibiotic resistance among human pathogenic microorganisms and the failure of conventional cancer therapies attracting great attention among scientists in the field of herbal medicine to develop natural antimicrobial and anticancer drugs. Thus, the antimicrobial and anticancer activities from fruits of the medicinal plant Urginea maritima (L.) Baker that unexplored previously were investigated in this study. Materials and Methods: Fruits of U. maritima plant were collected, dried, ground, and extracted by hot water, ethanol, methanol, and acetone. The fruit extracts were examined for their potential as antimicrobial and anticancer agents using the agar well diffusion method and MTT assay, respectively. The gene expression of some cancer-related gene markers was determined by RT-PCR. Results: All fruit extracts of U. maritima exhibited antibacterial activity against S. aureus and E. coli. Methanol and ethanol extracts exhibited anticandidal activity. Ethanol and acetone extracts displayed non-hemolytic activity and selective cytotoxicity against breast cancer MCF7 cells with IC 50 values that considered as active treatments. Concerning DNA fragmentation and gene expression after treatment of MCF7 cells with the most promising acetone extract, induction of apoptosis was proposed. The expression of cancer-related gene TNF after 6 hours, tumor suppressor genes (p53 and BRCA1), and immune response genes (IL-2 and IL-6) was induced. The expression of antiapoptotic gene Bcl2 in treated MCF7 cells was reduced. Conclusion: Fruit extracts of U. maritima exhibited antimicrobial and anticancer activities. This result may lead to the use of these extracts for treatment of some infectious diseases and certain types of cancer.

Varthemia iphionoides is a Jordanian medicinal plant with several health-promoting properties, including antibacterial, antioxidant and anticancer activities. However, its anti-inflammatory properties have been poorly investigated up to date. The current study aimed to investigate the anti-inflammatory effect of V. iphionoides by measuring the production of interleukin-6 in response to a pro-inflammatory stimulus (bacterial lipopolysaccharide) in in vitro cell models of human MRC-5 and PC3 cells. We observed a significant reduction in lipopolysaccharide-induced interleukin-6 release in response to V. iphionoides (125 µg/mL) in both non-cancerous fibroblast MRC-5 and prostate cancerous PC3 cells. However, the anti-inflammatory effect of this medicinal plant was stronger when MRC-5 cells were treated with an aqueous extract, while the methanolic extract was more potent in PC3 cells. The effect of V. iphionoides in reducing interleukin-6 production was not due to its cytotoxicity, and future studies are required to elucidate the mechanisms of action by which this medicinal plant modulates inflammatory responses. In conclusion, the results of our study represent the first report of the potential protective effect of water and methanolic extracts of V. iphionoides against pro-inflammatory stimuli in fibroblasts and cancer cells of human origin, and it is critically important to identify the phytochemical compounds responsible for this effect.