Sensitivity of tumor cells towards CIGB‐300 anticancer peptide relies on its nucleolar localization

CIGB‐300 is a novel anticancer peptide that impairs the casein kinase 2‐mediated phosphorylation by direct binding to the conserved phosphoacceptor site on their substrates. Previous findings indicated that CIGB‐300 inhibits tumor cell proliferation in vitro and induces tumor growth delay in vivo in cancer animal models. Interestingly, we had previously demonstrated that the putative oncogene B23/nucleophosmin (NPM) is the major intracellular target for CIGB‐300 in a sensitive human lung cancer cell line. However, the ability of this peptide to target B23/NPM in cancer cells with differential CIGB‐300 response phenotype remained to be determined. Interestingly, in this work, we evidenced that CIGB‐300's antiproliferative activity on tumor cells strongly correlates with its nucleolar localization, the main subcellular localization of the previously identified B23/NPM target. Likewise, using CIGB‐300 equipotent doses (concentration that inhibits 50% of proliferation), we demonstrated that this peptide interacts and inhibits B23/NPM phosphorylation in different cancer cell lines as evidenced by in vivo pull‐down and metabolic labeling experiments. Moreover, such inhibition was followed by a fast apoptosis on CIGB‐300‐treated cells and also an impairment of cell cycle progression mainly after 5 h of treatment. Altogether, our data not only validates B23/NPM as a main target for CIGB‐300 in cancer cells but also provides the first experimental clues to explain their differential antiproliferative response. Importantly, our findings suggest that further improvements to this cell penetrating peptide‐based drug should entail its more efficient intracellular delivery at such subcellular localization. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.     

A comparison of force fields for ethanol–water mixtures

Aqueous ethanol mixtures are studied through molecular dynamics simulations with the focus on exploring how various force field models reproduce the association and its influence on selected thermo-physical properties of these mixtures. The most important conclusion seems to be the inadequacy of all classical force fields to reproduce the very peculiar shape of the excess enthalpy of these mixtures, as a function of the ethanol concentration, neither quantitatively nor qualitatively. The Kirkwood–Buff (KB) integrals calculated using the simulation data follow the same trends as the experimental ones. This suggests complicated correlation of the excess enthalpy with the concentration fluctuation and clustering in these mixtures. The KB force field shows better overall agreement with experimental results than the other studied models.     

Multiple Niche Compartments Orchestrate Stepwise Germline Stem Cell Progeny Differentiation

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