Circular Dichroism as a Tool of Investigation in the B-Z Transition of DNA

Some useful CD applications aiming to investigate the B-Z conformational change in nucleic acids as well as their inter actions with a ruthenium complex of potential terapeutic interest are described in this paper. The results presented here regard: a) the energetics of the conformational transition from the B right-handed to the Z left-handed helix in synthetic oligodeoxynucleotides with a cytosine-guanine alternating sequence; b) The B to Z transition for sequences containing all four canonical bases and the role of nickel ions and sodium perchlorate in promoting this tranformation; c) the inter action of Ru(II)(DMSO)4CI2a. compound exhibiting a good antitumor activity in animals, with both mononucleosides and polynucleotides

Circular Dichroism as a Tool of Investigation in the B-Z Transition of DNA

Some useful CD applications aiming to investigate the B-Z conformational change in nucleic acids as well as their inter actions with a ruthenium complex of potential terapeutic interest are described in this paper. The results presented here regard: a) the energetics of the conformational transition from the B right-handed to the Z left-handed helix in synthetic oligodeoxynucleotides with a cytosine-guanine alternating sequence; b) The B to Z transition for sequences containing all four canonical bases and the role of nickel ions and sodium perchlorate in promoting this tranformation; c) the inter action of Ru(II)(DMSO)4CI2a. compound exhibiting a good antitumor activity in animals, with both mononucleosides and polynucleotides

Efficient Silencing of bcr/abl Oncogene by Single- and Double-Stranded siRNAs Targeted against b2a2 Transcripts †

ABSTRACT: In this work, double- and single-stranded small-interference RNAs (siRNAs) were designed to knock down the bcr/abl oncogene in leukaemia KYO-1 cells. The siRNA molecules were targeted against two distinct sites encompassing the b2a2 junction of the bcr/abl transcripts. The siRNAs were able to reduce the levels of both bcr/abl mRNA and protein p210 BCR/ABL. Conversely, control siRNAs bearing 3 or 4 base-pair substitutions did not produce any inhibitory effect. The designed siRNAs were also found to be active in KCl22 cells, which harbor the b2a2 junction, but not in K562 cells, which, by contrast, harbor the b3a2 junction. The anti-b2a2 siRNAs promoted biological effects on KYO-1 cells, because the bcr/abl suppression resulted in the inhibition of cell growth and colony formation in agar and activation of apoptosis and upregulation of the cell-cycle inhibitor p27 protein. The bioactivity of the designed siRNAs is discussed in terms of internal stability of the RNA duplexes. Our data suggest that siRNAs can be considered strong tools for functional analysis of bcr/abl and for developing molecular therapeutic approaches to leukaemia. A reciprocal translocation between chromosomes 9 and 22, t(9;22), is found in more than 95 % of patients with chronic myeloid leukaemia (CML) 1 and in about 20 % o

The Role Of Nitric Oxide After Repeated Low Dose Photodynamic Treatments In Prostate Carcinoma Cells

Photodynamic therapy (PDT) is a clinically approved treatment that causes a selective cytotoxic effect in cancer cells. In addition to the production of singlet oxygen and reactive oxygen species, PDT can induce the release of nitric oxide (NO) by up-regulating nitric oxide synthases (NOS). Since non-optimal PDT often causes tumor recurrence, understanding of the molecular pathways involved in the photoprocess is a challenging task for scientists. The present study has examined the response of the PC3 human metastatic prostate cancer cell line, following repeated low-dose pheophorbide a treatments, mimicking non-optimal PDT treatment. The analysis was focused on the NF-kB/YY1/RKIP circuitry as it is (i) dysregulated in cancer cells (ii) modulated by NO and (iii) correlated with the epithelial to mesenchymal transition (EMT). We hypothesized that a repeated treatment of non-optimal PDT induces low levels of NO that lead to cell growth and EMT via regulation of the above circuitry. The expressions of gene products involved in the circuitry and in EMT were analyzed by western blot. The findings demonstrate the cytoprotective role of NO following non-optimal PDT treatments that was corroborated by the use of l-NAME, an inhibitor of NOS