C5 Extract Induces Apoptosis in B16F10 Murine Melanoma Cells through Extrinsic and Intrinsic Apoptotic Pathways and Sub-G1 Phase Arrest

Purpose: To investigate the anti-cancer activities of C5 extract (C5E), a new herbal preparation from Korea, on B16F10 cells.Methods: The anti-proliferative effects of C5E were assessed by culturing B16F10 cells in the presence or absence of C5E. Cell cycle progression was analyzed by PI staining using flow cytometry. The quantities of apoptosis-inducing proteins were measured by Western blot.Results: C5E inhibited the proliferation of B16F10 cells but not human keratinocytes. C5E induced S phase arrest by interfering with cell regulatory factors such as cyclins B1, D1, D3, and E, and cyclindependent kinase 2, in B16F10 cells. Furthermore, immunoblot analysis confirmed that treatment with C5E induced apoptosis and cleaved caspase-3, poly (ADP-ribose) polymerase, via extrinsic pathway, whereas Bcl-2 expression was down-regulated. In addition, the suppression of cell proliferation by C5E is through down-regulation of p-Akt, up-regulation of phosphatase and tensin homolog protein expression via phosphoinositol 3 kinase survival signaling pathways in B16F10 cells. The combined cytotoxic effects of C5E and vinblastine generated 10 % increase in activity in contrast to the sum of the inhibitory effects of the individual agents.Conclusion: C5E shows promising anti-cancer activity and can be a useful adjuvant with vinblastine in combination therapeutic treatment of skin cancer.Keywords: Melanoma, Apoptosis, Anti-cancer, p53, Vinblastine, Cell cycle arrest, Caspas

Sequence dependent exposure of mammary carcinoma cells to Taxotere® and the MEK1/2 inhibitor U0126 causes enhanced cell killing in vitro

Taxol (paclitaxel) and Taxotere (docetaxel) are considered as two of the most important anticancer chemotherapy drugs. The cytotoxic action of these drugs has been linked to their ability to inhibit microtubule depolymerization, causing growth arrest and subsequent cell death. Studies by a number of laboratories have also linked suppression of mitogen activated protein kinase (MAPK) signaling to enhanced Taxol toxicity. The present study examined the interactions of the semi-synthetic taxane Taxotere with MEK1/2 inhibitors in epithelial tumor cells. Concurrent treatment of MDA-MB-231 mammary and DU145 prostate carcinoma cells with Taxotere and MEK1/2 inhibitor resulted in protection from the anti-proliferative effects of Taxotere in MTT assays. In contrast, in MCF-7 mammary cells, concurrent Taxotere and MEK1/2 inhibitor treatment weakly enhanced the antiproliferative effects of the taxane. Sequential treatment of MDA-MB-231 and MCF-7 cells with Taxotere followed by MEK1/2 inhibitor also enhanced the anti-proliferative effects of the taxane in MTT assays. However, no enhancement was observed in DU145 or PC-3 cells. Colony formation assays, including isobologram analyses, provided a more definitive demonstration that MCF-7 and MDA-MB-231 cells were sensitized to the toxic effects of Taxotere by U0126. Similar data were observed using Laulimalide, which binds to tubulin at a different site to Taxotere. The enhancement in Taxotere anti-proliferative effects by U0126 correlated with increased cell killing, 48-72h after treatment of cells that was blocked by inhibition of caspase 9, but not caspase 8, function. This observation was associated with prolonged suppression of ERK1/2 and AKT activity, without alteration in either p38 or JNK1/2 activity. Collectively these findings demonstrate that sequential administration of Taxotere followed by MEK1/2 inhibition can lead to increased cell death and loss of reproductive capacity in some, but not all, human tumor cells. ©2003 Landes Bioscience.Fil: Yacoub, Adly. Virginia Commonwealth University; Estados UnidosFil: Han, Song Iy. Virginia Commonwealth University; Estados UnidosFil: Caron, Ruben Walter. Virginia Commonwealth University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Gilfor, Donna. Virginia Commonwealth University; Estados UnidosFil: Mooberry, Susan. Southwest Foundation for Biomedical Research; Estados UnidosFil: Grant, Steven. Virginia Commonwealth University; Estados UnidosFil: Dent, Paul. Virginia Commonwealth University; Estados Unido

Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis

<p>Abstract</p> <p>Background</p> <p>In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1), and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood.</p> <p>Results</p> <p>In the present study, we show that Distal-less 2 (Dlx-2), a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS) in response to glucose deprivation (GD), one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an <it>in vitro </it>model of solid tumors. Dlx-2 short hairpin RNA (shRNA) inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH) release, indicating the important role(s) of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis.</p> <p>Conclusions</p> <p>These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.</p

Direct nitrogen fixation at the edges of graphene nanoplatelets as efficient electrocatalysts for energy conversion

Nitrogen fixation is essential for the synthesis of many important chemicals (e.g., fertilizers, explosives) and basic building blocks for all forms of life (e.g., nucleotides for DNA and RNA, amino acids for proteins). However, direct nitrogen fixation is challenging as nitrogen (N2) does not easily react with other chemicals. By dry ball-milling graphite with N2, we have discovered a simple, but versatile, scalable and eco-friendly, approach to direct fixation of N2 at the edges of graphene nanoplatelets (GnPs). The mechanochemical cracking of graphitic C-C bonds generated active carbon species that react directly with N2 to form five- and six-membered aromatic rings at the broken edges, leading to solution-processable edge-nitrogenated graphene nanoplatelets (NGnPs) with superb catalytic performance in both dye-sensitized solar cells and fuel cells to replace conventional Pt-based catalysts for energy conversion.open302

Regulation of the Cardiac Na+/K+ ATPase by Phospholemman

Hansraj Dhayan, Rajender Kumar, Andreas Kukol, ‘Regulation of the Cardiac Na+/K+ ATPase by Phospholemman’, in Sajal Chakraborti, Naranjan Dhalla, eds., Regulation of Membrane Na+-K+ ATPase, (Switzerland: Springer, 2016), ISBN 978-3-319-24748-9, eISBN 978-3-319-24750-2.Peer reviewe

Regulation of Tumor Progression by Programmed Necrosis

Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g., glucose) deprivation, which occurs because of insufficient blood supply. This results in necrotic cell death in the core region of solid tumors. Necrotic cells release their cellular cytoplasmic contents into the extracellular space, such as high mobility group box 1 (HMGB1), which is a nonhistone nuclear protein, but acts as a proinflammatory and tumor-promoting cytokine when released by necrotic cells. These released molecules recruit immune and inflammatory cells, which exert tumor-promoting activity by inducing angiogenesis, proliferation, and invasion. Development of a necrotic core in cancer patients is also associated with poor prognosis. Conventionally, necrosis has been thought of as an unregulated process, unlike programmed cell death processes like apoptosis and autophagy. Recently, necrosis has been recognized as a programmed cell death, encompassing processes such as oncosis, necroptosis, and others. Metabolic stress-induced necrosis and its regulatory mechanisms have been poorly investigated until recently. Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2 contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s) in initiating necrosis. Here, we discuss the molecular mechanisms underlying metabolic stress-induced programmed necrosis that promote tumor progression and aggressiveness

Selection of a core set of RILs from Forrest × Williams 82 to develop a framework map in soybean

Soybean BAC-based physical maps provide a useful platform for gene and QTL map-based cloning, EST mapping, marker development, genome sequencing, and comparative genomic research. Soybean physical maps for “Forrest” and “Williams 82” representing the southern and northern US soybean germplasm base, respectively, have been constructed with different fingerprinting methods. These physical maps are complementary for coverage of gaps on the 20 soybean linkage groups. More than 5,000 genetic markers have been anchored onto the Williams 82 physical map, but only a limited number of markers have been anchored to the Forrest physical map. A mapping population of Forrest × Williams 82 made up of 1,025 F8 recombinant inbred lines (RILs) was used to construct a reference genetic map. A framework map with almost 1,000 genetic markers was constructed using a core set of these RILs. The core set of the population was evaluated with the theoretical population using equality, symmetry and representativeness tests. A high-resolution genetic map will allow integration and utilization of the physical maps to target QTL regions of interest, and to place a larger number of markers into a map in a more efficient way using a core set of RILs

Fe3O4–Au and Fe2O3–Au Hybrid Nanorods: Layer-by-Layer Assembly Synthesis and Their Magnetic and Optical Properties

A layer-by-layer technique has been developed to synthesize FeOOH–Au hybrid nanorods that can be transformed into Fe2O3–Au and Fe3O4–Au hybrid nanorods via controllable annealing process. The homogenous deposition of Au nanoparticles onto the surface of FeOOH nanorods can be attributed to the strong electrostatic attraction between metal ions and polyelectrolyte-modified FeOOH nanorods. The annealing atmosphere controls the phase transformation from FeOOH–Au to Fe3O4–Au and α-Fe2O3–Au. Moreover, the magnetic and optical properties of as-synthesized Fe2O3–Au and Fe3O4–Au hybrid nanorods have been investigated