1,721,003 research outputs found
Potent Apoptotic Response Induced by Chloroacetamidine Anthrathiophenediones in Bladder Cancer Cells.
Full text linkWe previously found that two neighboring G-quadruplexes behave as a molecular switch controlling the expression of HRAS (Cogoi, S.; Schekotikhin, A. E.; Xodo, L. E. Nucl. Acids Res. 2014, DOI: 10.1093/nar/gku574). In this study we have designed anthrathiophenediones with two hloroacetamidine-containing side chains (CATDs) as G-quadruplex binders and have examined their anticancer activity in T24 bladder cancer cells bearing mutant HRAS and in T24 xenografts. The designed CATDs (3a−e), bearing alkyl side chains of different length, penetrate T24 cancer cells more than their analogues with guanidine-containing side chains. The lead compounds 3a and 3c inhibit HRAS expression, metabolic activity, and colony formation in T24 cancer cells. They also activate a strong apoptotic response, as indicated by PARP-1, caspases 3/7, and annexin V/propidium iodide assays.
Apoptosis occurs under conditions where cyclin D1 is down-regulated and the cell cycle arrested in G2 phase. Finally, compound 3a inhibits the growth of T24 xenografts and increases the median survival time of nude mice
Role of RKIP in the tumor response to photooxidative damage
No full textThe Raf-kinase inhibitor protein (RKIP) plays a role in the regulation of different processes, through its interaction with several signaling pathways. These pathways include the mitogen activated protein kinase (MAPK), nuclear factor kappa-light chain enhancer of activated B cells (NF-κB), G protein-coupled receptors (GPCR) and glycogen synthase kinase 3 beta (GSK 3β). RKIP negatively affects tumor survival and proliferation, acting as a metastasis suppressor. Moreover, RKIP overexpression has been reported to reverse tumor chemo/immuno/radio-resistance and support the anticancer host immuno-surveillance. The aim of this work is to evaluate the role of RKIP in cancer cells during a photooxidative damage induced by photodynamic therapy (PDT). PDT treatment is based on three components: a photosensitizer, light and oxygen. Their combined action produces singlet oxygen (1O2) and/or reactive oxygen species (ROS) leading to an oxidative insult in tumor cells. Dependently on the PDT dose, the response of tumor cells can have a double outcome: stimulation of tumor cell proliferation with a low PDT dose (IC50), or tumor growth arrest in the case of a high PDT dose (IC50). We evaluated RKIP expression within its complex network, correlating with other factors involved in the tumor response to oxidative stress. We found a link between the expression of RKIP and NF-κB, MAPK, Snail and Nrf2 according to the type of the oxidative insult. In the presence of low PDT, RKIP is downregulated, while NF-κB, Snail and Nrf2 are upregulated: an expression profile that stimulates tumor proliferation and resistance. Conversely, RKIP is overexpressed in the case of high PDT, thus allowing an arrest of tumor growth.Considering that many antitumor drugs develop ROS/RNS causing disease recurrence and drug resistance, RKIP could be a good prognostic marker to follow patients' response to anticancer therapies
The ROS-KRAS-Nrf2 axis in the control of the redox homeostasis and the intersection with survival-apoptosis pathways: Implications for photodynamic therapy
No full textBystander effect in photosensitized prostate cancer cells with a different grade of malignancy: The role of nitric oxide
No full textPhotodynamic therapy (PDT) is a therapeutic modality based on the simultaneous action of three elements: photosensitizer, light and oxygen. This triad generates singlet oxygen and reactive oxygen species that can reduce the mass of a tumor. PDT is also able to stimulate iNOS, the enzyme that generates nitric oxide (NO). The role of NO in PDT-treated cancer cells has been investigated in several studies. They showed that low iNOS/NO levels stimulate signaling pathways that promote tumor survival, while high iNOS/NO levels arrest tumor growth. There is increasing evidence that ROS/RNS control both proliferation and migration of cells in the vicinity of PDT-treated tumor cells (so-called bystander cells). In this work, we addressed the question of how NO, which is generated by weak PDT, affects bystander cells. We used a conditioned medium: medium of PDT-treated tumor cells containing the stressors produced by the cells was added to untreated cells mimicking the neighboring bystander cells to investigate whether the conditioned medium affects cell proliferation. We found that low-level NO in prostate cancer cells affects the bystander tumor cells in a manner that depends on their malignancy grade
Widespread presence in mammals and high binding specificity of a nuclear protein that recognizes the single-stranded (CCCTAA)n telomeric motif.
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Formation of stable DNA triple helices within the human bcr promoter at a critical oligopurine target interrupted in the middle by two adjacent pyrimidines.
No full textANTISENSE NUCLEIC ACIDS DRUGS DEVELOPMEN
Inhibition of T7 RNA polymerase transcription by phosphate and phosphorothioate triplex-forming oligonucleotides targeted to a R.Y site downstream from the promoter.
No full textSmall Interfering RNA-Mediated Silencing of Glutathione-S-transferase A1 Sensitizes Hepatic Carcinoma Cells to Photodynamic Therapy with Pentaphyrins
No full textPhotodynamic therapy (PDT) uses nontoxic photosensitizers and visible light to produce reactive oxygen species that kill malignant cells by apoptosis or necrosis. Silencing the antioxidant GSTA1-1 gene by siRNA sensitizes hepatic HepG2 cells to PDT with pentaphyrins. The study is a proof-of-concept for combining PDT with antigene molecules that decrease cellular response to oxidative stress
Sequence-specific DNA-triplex formation at imperfect homopurine-homopyrimidine sequences within a DNA plasmid
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