Combined effect of silver nanoparticles and aluminium chloride, butylparaben or diethylphthalate on the malignancy of MDA-MB-231 breast cancer cells and tumor-specific immune responses of human macrophages and monocyte-derived dendritic cells
TOXICOLOGY IN VITRO
Authors: Roszak, Joanna; Smok-Pieniazek, Anna; Jezak, Karolina; Domeradzka-Gajda, Katarzyna; Grobelny, Jaroslaw; Tomaszewska, Emilia; Ranoszek-Soliwoda, Katarzyna; Celichowski, Grzegorz; Stepnik, Maciej
Abstract
The aim of this study was to assess whether silver nanoparticles (AgNP) or selected cosmetic ingredients may modify functions of various immunocompetent cell populations. To this end, the effect of two AgNP (size of 15 nm or 45 nm), alone and in combination with aluminium chloride, butyl paraben, di-n-butyl phthalate or diethyl phthalate was assessed on: (1) migration and invasion of MDA-MB-231 human breast cancer cells; (2) M1/M2 polarization of phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages (MO) and (3) activation/maturation of monocyte-derived dendritic cells (DCs). The results of this study showed that neither any of the test chemicals alone nor the mixtures significantly changed the migration or invasion ability of MDAMB-231 cells following, both 72-h and 21-day exposure. Analysis of the expression of marker genes for both M1 (IL-1B, CXCL9, TNF) and M2 (DCSIGN, MRC1) polarization revealed that the chemicals/mixtures did not activate M1/M2 differentiation of the MO macrophages. In addition, no significant changes were observed in the expression of CD86, HLA-DR and CD54 surface markers and phagocytic activity of DCs following 48-h exposure to AgNP alone or in combination with test compounds.
The Human Tim-Tipin Complex Interacts Directly with DNA Polymerase epsilon and Stimulates Its Synthetic Activity
JOURNAL OF BIOLOGICAL CHEMISTRY
Authors: Aria, Valentina; De Felice, Mariarita; Di Perna, Roberta; Uno, Shuji; Masai, Hisao; Syvaoja, Juhani E.; van Loon, Barbara; Huebscher, Ulrich; Pisani, Francesca M.
Abstract
The Tim-Tipin complex plays an important role in the S phase checkpoint and replication fork stability in metazoans, but the molecular mechanism underlying its biological function is poorly understood. Here, we present evidence that the recombinant human Tim-Tipin complex (and Tim alone) markedly enhances the synthetic activity of DNA polymerase epsilon. In contrast, no significant effect on the synthetic ability of human DNA polymerase alpha and delta by Tim-Tipin was observed. Surface plasmon resonance measurements and co-immunoprecipitation experiments revealed that recombinant DNA polymerase epsilon directly interacts with either Tim or Tipin. In addition, the results of DNA band shift assays suggest that the Tim-Tipin complex (or Tim alone) is able to associate with DNA polymerase epsilon bound to a 40-/80-mer DNA ligand. Our results are discussed in view of the molecular dynamics at the human DNA replication fork.