Cell Polarity: A Link to Epithelial-Mesenchymal Transition and Vascular Mimicry.

Cell polarity is an essential process for development, cell physiology and tissue homeostasis. Loss of cell polarity is a characteristic feature of cancer. This review highlights the factors involved in maintenance of cell polarity and looks at the link between cell polarity, epithelial mesenchymal transition (EMT) and cancer and finally tries to draw link between cell polarity and vascular mimicry in EMT occurring cells.

Events of Molecular Changes in Epithelial-Mesenchymal Transition.

EMT is the process by which epithelial cells, characterized by well-developed intercellular contacts, transdifferentiate into motile and invasive mesenchymal cells. This process is associated with the loss of transmembrane intercellular adhesion molecule E-cadherin and disruption of cell-cell junctions along with acquisition of migratory properties. EMT is integral in embryonic development, wound healing, and stem cell behavior; however, its aberrant activation by micro-environmental alterations and abnormal stimuli can lead to cancer progression. Here, we review the different molecular changes associated with EMT that are responsible for downregulation of epithelial genes. Increased knowledge of the EMT process is essential for therapeutic targeting of cancer cells.

Epithelial Mesenchymal Transition and Vascular Mimicry in Breast Cancer Stem Cells.

Vasculogenic mimicry (VM), a newly defined pattern of tumor microvascularization differs from angiogenesis and vasculogenesis in its noninvolvement of endothelial cells, by which highly aggressive tumor cells can form vessel-like structures themselves, because of their high plasticity. The presence of VM has been shown to be strongly associated with a poor prognosis in several types of cancer, but biological features of tumor cells that form VM remains unknown. Human breast cancer, characterized by a group of highly heterogeneous lesions, is the most common cancer in women and one of the leading causes of cancer-related deaths worldwide. The epithelialmesenchymal transition (EMT) state in breast cancer has been associated with cancer stem cell (CSC) properties, self-renewal capabilities, resistance to conventional therapies, and a tendency for posttreatment recurrence. With increasing knowledge about cancer stem cell phenotypes and functions, they are implicated in VM formation. Studies also indicate that EMT is relevant to the acquisition and maintenance of stem cell-like characteristics and is involved in VM. This review discusses the correlation between CSCs, EMT, and VM formation with a focus on breast cancer. Also, the signalling molecules and pathways involved in VM and some recently defined direct VM targeting strategies in breast cancer are reviewed here.

Breast cancer stem cells, EMT and therapeutic targets.

A small heterogeneous population of breast cancer cells acts as seeds to induce new tumor growth. These seeds or breast cancer stem cells (BCSCs) exhibit great phenotypical plasticity which allows them to undergo "epithelial to mesenchymal transition" (EMT) at the site of primary tumor and a future reverse transition. Apart from metastasis they are also responsible for maintaining the tumor and conferring it with drug and radiation resistance and a tendency for post-treatment relapse. Many of the signaling pathways involved in induction of EMT are involved in CSC generation and regulation. Here we are briefly reviewing the mechanism of TGF-ß, Wnt, Notch, TNF-α, NF-κB, RTK signalling pathways which are involved in EMT as well as BCSCs maintenance. Therapeutic targeting or inhibition of the key/accessory players of these pathways could control growth of BCSCs and hence malignant cancer. Additionally several miRNAs are dysregulated in cancer stem cells indicating their roles as oncogenes or tumor suppressors. This review also lists the miRNA interactions identified in BCSCs and discusses on some newly identified targets in the BCSC regulatory pathways like SHIP2, nicastrin, Pin 1, IGF-1R, pro-inflammatory cytokines and syndecan which can be targeted for therapeutic achievements.

Evaluation of Antibacterial Activity of Lactobacillus Spp. on Selected Food Spoilage Bacteria.

This study was done to isolate Lactobacillus species from curd, amla/Indian gooseberry and orange and to assess their antagonistic ability against selected food spoilage bacteria, Escherichia coli, Pseudomonas spp. and Bacillus spp. isolated from natural food sources. In the approaches used, native Lactobacillus spp. were isolated from amla, orange and curd and identified by standard microbiological methods. Their antagonistic affect was tested by disc diffusion tests against three selected test isolates, Escherichia coli, Pseudomonas and Bacillus spp. isolated from tomato, pumpkin, cauliflower, lady's finger, carrot, and milk. There are recent patents also suggesting use of novel strains of Lactobacillus for microbial antagonism. In our present work, the lactobacilli isolated from different food sources showed varied ability to inhibit the growth of test isolates. The growth of test isolates was inhibited by Lactobacillus isolates with one of the Lactobacillus isolate from amla being the most potent inhibitor.

An assessment of norepinephrine mediated hypertrophy to apoptosis transition in cardiac cells: a signal for cell death.

OBJECTIVES: Heart is an organ which is under a constant work load that generates numerous stress responses. Heart failure is associated with increased plasma norepinephrine (NE) and hypertrophic cell death. Within the current study we try to understand the concentration dependent molecular switch from hypertrophy to apoptosis under stress. METHODS: The effect of increasing concentration of NE on cell death was studied using MTT assay based on which further experimental conditions were decided. Trypan Blue staining and TUNEL assay were done at selected concentrations of NE. Cellular and nuclear morphology at these concentrations was studied using Haematoxylin-Eosin, DAPI and PI stains. The molecular switch between hypertrophy and cell death was studied by expression analysis of ß-MyHC and TNF-α. Rhodamine and DCFH-DA staining were done to evaluate the role of mitochondria and ROS under these conditions. Role of caspases under these transitions was also evaluated. RESULT: NE shows steep falls in cell viability at 50 µM and 100 µM concentrations. The cellular and nuclear morphology is altered at these concentrations along with alterations at molecular level showing a shift from hypertrophy towards cell death. Altered mitochondrial membrane potential and increase in ROS support this which leads to caspase dependent activation of cell death. CONCLUSION: We show that at 50 µM NE, there occurs a transition from cellular hypertrophy towards death. This could be beneficial to prevent hypertrophy induced cardiac cell death and evaluating cardio protective therapeutic targets in vitro.

Green synthesis of silver nanoparticles: an approach to overcome toxicity.

Nanotechnology, with its advent, has made deep inroads into therapeutics. It has revolutionized conventional approaches in drug designing and delivery systems by creating a large array of nanoparticles that can pass even through relatively impermeable membranes such as blood brain barrier. Like the two sides of a coin, nanotechnology too has its own share of disadvantages which in this scenario is the toxicology of these nanoparticles. Numerous studies have discussed the toxicity of various nanoparticles and the recent advancements done in the field of nanotechnology is to make it less toxic. "Green synthesis" of nanoparticles is one such approach. The review summarizes the toxicity associated with the nanoparticles and the advancement of "green" nanomaterials to resolve the toxicity issues.

Cardioprotective role of Syzygium cumini against glucose-induced oxidative stress in H9C2 cardiac myocytes.

Diabetic patients are known to have an independent risk of cardiomyopathy. Hyperglycemia leads to upregulation of reactive oxygen species (ROS) that may contribute to diabetic cardiomyopathy. Thus, agents that suppress glucose-induced intracellular ROS levels can have therapeutic potential against diabetic cardiomyopathy. Syzygium cumini is well known for its anti-diabetic potential, but its cardioprotective properties have not been evaluated yet. The aim of the present study is to analyze cardioprotective properties of methanolic seed extract (MSE) of S. cumini in diabetic in vitro conditions. ROS scavenging activity of MSE was studied in glucose-stressed H9C2 cardiac myoblasts after optimizing the safe dose of glucose and MSE by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide. 2',7'-dichlorfluorescein diacetate staining and Fluorescence-activated cell sorting analysis confirmed the suppression of ROS production by MSE in glucose-induced cells. The intracellular NO and H2O2 radical-scavenging activity of MSE was found to be significantly high in glucose-induced cells. Exposure of glucose-stressed H9C2 cells to MSE showed decline in the activity of catalase and superoxide dismutase enzymes and collagen content. 4',6-diamidino-2-phenylindole, propidium iodide and 10-N-nonyl-3,6-bis (dimethylamino) acridine staining revealed that MSE protects myocardial cells from glucose-induced stress. Taken together, our findings revealed that the well-known anti-diabetic S. cumini can also protect the cardiac cells from glucose-induced stress.

Cloning and expression of human islet amyloid polypeptide in cultured cells.

Efforts to clone amyloidogenic proteins in the cells often have resulted in cell death. We report successful cloning and expression of recombinant human islet amyloid polypeptide (hIAPP) in cultured mammalian cells. Amylin gets secreted, forms fibrils that are toxic to target cells like beta cells of rat and human. The study involves cloning of full-length amylin in fluorescent protein vector followed by transfection into mammalian cells. The transfected cells with recombinant human amylin, secrete the translated protein corresponding to 37-amino acid native mature IAPP. The mature IAPP secreted out of the cell is purified and characterized by MALDI-TOF/TOF-MS and Western blotting. Purified IAPP forms fibrils as seen by Thioflavin-T fluorescence and AFM, and these fibrils were cytotoxic towards pancreatic cell line RIN5mf cells.