SU5416 and EGCG Work Synergistically and Inhibit Angiogenic and Survival Factors and Induce Cell Cycle Arrest to Promote Apoptosis in Human Malignant Neuroblastoma SH-SY5Y and SK-N-BE2 Cells

Malignant neuroblastomas are solid tumors in children. Available therapeutic agents are not highly effective for treatment of malignant neuroblastomas. Therefore, new treatment strategies are urgently needed. We tested the efficacy of combination of SU5416 (SU), an inhibitor of the vascular endothelial growth factor receptor-2 (VEGFR-2), and (−)-epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, for controlling growth of human malignant neuroblastoma SH-SY5Y and SK-N-BE2 cells. Combination of 20 μM SU and 50 μM EGCG synergistically inhibited cell survival, suppressed expression of VEGFR-2, inhibited cell migration, caused cell cycle arrest, and induced apoptosis. Combination of SU and EGCG effectively blocked angiogenic and survival pathways and modulated expression of cell cycle regulators. Apoptosis was induced by down regulation of Bcl-2, activation of caspase-3, and cleavage of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP). Taken together, this combination of drugs can be a promising therapeutic strategy for controlling the growth of human malignant neuroblastoma cells.     

Inactivation of PTEN is responsible for the survival of Hep G2 cells in response to etoposide-induced damage

The chemo-resistance character of human hepatocellular carcinoma cells is well known but the anomalies associated with such resistance character are not completely understood. In this study, etoposide-induced signaling events in human hepatocellular carcinoma cell line, Hep G2 has been compared with Chang Liver cells, a normal human liver cell line. Hep G2 cells are resistant to etoposide when compared with Chang Liver cells. Etoposide-induced γH2AX foci in Hep G2 cells are persisted for a longer time without affecting cell cycle, indicating that Hep G2 cells are able to maintain its growth with damaged DNA. Further, Akt signaling pathway is deregulated in Hep G2 cells. The upstream negative regulator of Akt, PTEN remains inactive, as it is hyperphosphorylated in Hep G2 cells. Inhibition of PI-3K pathway by wortmannin partially reverses the etoposide-resistance character of Hep G2 cells. Either Hep G2 or Chang Liver cells when transfected with plasmid carrying active Akt (myr-Akt) become resistance towards etoposide compared to the cells transfected with empty vectors or kinase defective Akt. Transient transfection of wild type PTEN in Hep G2 cells does not change its response towards etoposide whereas Chang Liver cells become sensitive after transfection with same plasmid. These results suggest that inactivation of PTEN, which renders activation of Akt, may contribute largely for the etoposide-resistance character of Hep G2 cells.     

Bionomics of <Emphasis Type="Italic">Momordica cochinchinensis</Emphasis> Fed <Emphasis Type="Italic">Aulacophora foveicollis</Emphasis> (Coleoptera: Chrysomelidae)

The effects of feeding on root by the larvae and three types of Momordica cochinchinensis Spreng (Cucubitaceae) leaves (young, mature and senescent) by the adults of Aulacophora foveicollis Lucas (Coleoptera: Chrysomelidae) were studied under laboratory conditions. Total larval developmental time was 19.7 ± 0.2 days by feeding on young roots. Adult males lived for 28.4 ± 1, 65.7 ± 1.1 and 22.8 ± 1.3 days on young, mature and senescent leaves, respectively; whilst adult females lived for 34.3 ± 1.2, 68.5 ± 0.9 and 26.4 ± 1.4 days on young, mature and senescent leaves, respectively. Fecundity was highest in mature leaves fed insects (202.2 ± 10.6). Total carbohydrate, protein, lipid, nitrogen and amino acid were much higher in root followed by mature leaves than young and senescent leaves. Moisture content was highest in mature leaves than the roots, young and senescent leaves. Phenols were greatest in young leaves followed by mature leaves and least in senescent leaves and roots of the said plant. Flavonols were higher in young leaves and least in root. These results suggest that A. foveicollis adults perform better on mature leaves than young and senescent leaves for their nutrition.     

On the propensity of phosphatidylglycerols to form interdigitated phases

We have determined the phase behavior of disaturated phosphatidylglycerols (PGs) of chain lengths n(CH2) = 14-18 at high pH and ionic strength using calorimetry, dilatometry, as well as x-ray diffraction. PGs with n(CH2) = 14 and 16 show thermotropic behavior similar to that of phosphatidylcholines (PCs). The area/lipid obtained in the gel phase is smaller than that reported for PCs despite the expected larger effective headgroup size. This can be explained by the tilting of the PG headgroup out of the bilayer plane, and we provide experimental evidence for a headgroup tilt transition. For distearoyl PG, we further find that the "usual" gel phase coexists with an interdigitated phase, which exhibits a transition from an orthorhombic into a hexagonal chain packing. The total amount of the interdigitated phase depends significantly on the temperature but is found to be largely independent of temperature equilibration time and different sample preparation protocols. Thus, the development of the interdigitated phase appears to be kinetically trapped. The formation of interdigitated phases in PGs at much smaller chain lengths than in PCs is of high relevance to interaction studies with antimicrobial peptides, as it provides a mechanism for the discrimination of membranes composed of different lipid species.     

Floral biology,breeding system and pollination ecology of Justicia betonica L. (Acanthaceae): An assessment of its low reproductive success in West Bengal,India

Besides its importance as an ornamental plant, Justicia betonica L. is also used as a medicinal plant for the treatment of several human disorders. However, the population size and abundance of the plant species are very low in Indian states, including West Bengal. The breeding system and pollination ecology of J. betonica are still unclear. Therefore, some reproductive aspects were investigated in order to provide important information for the sustainability of the species. The flowering duration spanned from December to May, with its peak in February–March. Flower opening time was much earlier (5.00–8.00 a.m.) on a hot day (in April–May) than on a cold day (10.00 a.m.–12.00 p.m. in December–January). The time of anther dehiscence coincided with the flower opening time; however, the stigma became receptive later. The plant species is self-compatible but dependent on pollinators for fruit and seed sets. Members of different insect groups like ants, bees, butterflies, flies, moths and wasps visit the flowers. Among them, Allorhynchium metallicum and Halictus acrocephalus are the primary pollinators (based on the “relative pollinator service”). The plant species showed a significant pollination deficit (coefficient of pollination deficit [D] = 0.32) in the open condition. Larvae of the florivorous moth Gatesclarkeana erotias significantly reduced reproductive success by eating their floral parts, ovules and immature seeds. In conclusion, combining the pollination deficit and the feeding activity of phytophagous insects (moth larvae) may reduce the reproductive fitness of J. betonica in the study regions.     

Germline soma communication mediated by gap junction proteins regulates epithelial morphogenesis

Gap junction (GJ) proteins, the primary constituents of GJ channels, are conserved determinants of patterning. Canonically, a GJ channel, made up of two hemi-channels contributed by the neighboring cells, facilitates transport of metabolites/ions. Here we demonstrate the involvement of GJ proteins during cuboidal to squamous epithelial transition displayed by the anterior follicle cells (AFCs) from Drosophila ovaries. Somatically derived AFCs stretch and flatten when the adjacent germline cells start increasing in size. GJ proteins, Innexin2 (Inx2) and Innexin4 (Inx4), functioning in the AFCs and germline respectively, promote the shape transformation by modulating calcium levels in the AFCs. Our observations suggest that alterations in calcium flux potentiate STAT activity to influence actomyosin-based cytoskeleton, possibly resulting in disassembly of adherens junctions. Our data have uncovered sequential molecular events underlying the cuboidal to squamous shape transition and offer unique insight into how GJ proteins expressed in the neighboring cells contribute to morphogenetic processes.     

Galectin-1 signaling in leukocytes requires expression of complex-type N-glycans

Dimeric galectin-1 (dGal-1) is a homodimeric lectin with multiple proposed functions. Although dGal-1 binds to diverse glycans, it is unclear whether dGal-1 preferentially binds to specific subsets of glycans on cell surfaces to transmit signals. To explore this question, we selectively inhibited major glycan biosynthetic pathways in human HL60, Molt-4, and Jurkat cells. Inhibition of N-glycan processing blocked surface binding of dGal-1 and prevented dGal-1-induced Ca(2+) mobilization and phosphatidylserine exposure. By contrast, inhibition of O-glycan or glycosphingolipid biosynthesis did not affect dGal-1 binding or dGal-1-induced Ca(2+) mobilization and phosphatidylserine exposure. These results demonstrate that dGal-1 preferentially binds to and signals through glycoproteins containing complex-type N-glycans in at least some leukocyte subsets.