Purpose: Valproic acid (VPA) is used mainly for the treatment of epilepsy and other seizure disorders, however, it is known to be one of histone deacetylase (HDAC) inhibitors. HDACIs have represented roles in radiation-sensitizing of cancer cells. This study is aimed to study to evaluate the radiosensitizing capability of VPA in MCF-7 breast cancer cell line. Materials and Methods: Cell viability and apoptosis were assayed using MTT and TUNEL assays, respectively and caspase-8 and caspase-9 activities were measured by commercially available kits. Results: Our finding showed that pre treatment of cells with VPA, notably enhanced apoptotic cell death in MCF-7 cell line. Our results showed that VPA sensitizes cancer cells against radiation. Conclusion: Valproic acid could be a beneficial radio-sensitizer in breast cancer radiotherapy.

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Aim: Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive type of non-Hodgkin's lymphoma that accounts for ~40% of all lymphomas. DLBCL is considered to be clinically heterogeneous with highest mortality rate. Recent advances in gene expression profiling helped in identifying different subtypes of DLBCL, and since then, many therapeutic options have been explored to treat DLBCL patients. Although it is effective, a significant proportion of the patients suffer due to drug resistance. One of the potential causes for this could be elevated DNA repair in the resistant cancer cells. Thus, the present study is aimed at investigating the potential of SCR7, a DNA repair inhibitor in inducing cytotoxicity on a DLBCL cell line, and to study its ability to potentiate effect when used in combination with ionizing radiation. Materials and Methods: DLBCL cell line, Standford University Diffuse Histiocytic Lymphoma 8 (SUDHL8) was treated with various concentrations of SCR7, a DNA repair inhibitor that targets nonhomologous DNA end joining. While cytotoxicity induced by SCR7 was evaluated through trypan blue assay and flow cytometry analysis, 5,5',6,6 tetrachloro-1,1',3,3'-tetraethyl benzimidazol-carbocyanine iodide and annexin V-FITC/propidium iodide [PI] double-staining assays were used to study the mechanism of cell death. Modulation in the level of DNA repair and apoptotic proteins following treatment with SCR7 was examined by immunoblotting. Effect of SCR7 on sensitizing radiotherapy was further investigated in the SUDHL8 cells. Results: SCR7 induced cytotoxicity in the DLBCL cell line in a concentration- and time-dependent manner. Cell cycle analysis and annexin V/PI double-staining assay confirmed apoptosis in cells without interfering with cell cycle progression. Change in mitochondrial membrane potential in conjunction with alterations in the levels of apoptotic proteins suggested activation of both intrinsic and extrinsic pathways of apoptosis. Importantly, administration of SCR7 potentiated the effect of radiation upon combination therapy in DLBCL. Conclusion: Our results suggest that SCR7 could be developed as an alternative chemotherapeutic approach against DLBCL and is also effective along with radiotherapy.

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Many endogenous and exogenous sources produce reactive oxygen species such as superoxide radical anions and hydrogen peroxide that are converted to the highly reactive form, hydroxyl radical. It is this latter species that can damage several macromolecules in the cells, in particular, the DNA to produce a variety of DNA lesions. These DNA lesions include oxidatively damaged purine and pyrimidine bases, as well as single-strand and double-strand breaks. These unrepaired DNA lesions lead to base substitutions, deletions, insertions, and rearrangements of the chromosome, ultimately altering the stability of the genome. Maintaining the integrity of the genome is essential to prevent various diseases such as several types of cancers. There are several DNA repair pathways including base-excision repair (BER), nucleotide-excision repair, mismatch repair, homologous recombination, and nonhomologous end joining that operate in the human cells to prevent genomic instability. Each of these DNA repair pathways consists of multiple enzymes that execute specific function (s). This review focuses on a key enzyme apurinic/apyrimidinic endonuclease 1 (APE1) that belongs to the BER pathway that plays a pivotal role in the removal of modified DNA bases. We provide an overview of the multifaceted roles performed by APE1, which also serves as a redox factor and referred to as redox effector factor 1 (Ref-1) or APE1/Ref-1. In addition, we discuss more recent findings whereby (i) peroxiredoxin 1 controls the redox activity of APE1 and (ii) CUT-like homeobox 1 protein, a transcription factor that binds to DNA and stimulates the DNA repair activities of APE1 to confer resistance to radio- and chemotherapy.

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Context: It is analyzed whether genetic instability is determined by cell ability to recover from radiation damage or it is mainly determined by cell ploidy. The values of the RBE of α-particles for cell survival and genetic instability are obtained for haploid and diploid yeast cells. The delayed appearance of clones by cells surviving after exposure to γ-rays, α-particles, and UV-light are compared. Aim: To compare of genetic instability in haploid and diploid yeast cells exposed to ionizing radiations of different LET and UV light. Materials and Methods: Haploid (strain S288C, RAD) and homozygous diploid (strain XS800, RAD/RAD) yeast cells of Saccharomyces cerevisiae were used in our experiments. Cell survival and delayed clone appearance were studied for cells surviving after exposure to 60Co γ-rays, 239Pu α-particles and 254 nm UV light. Survival was determined by cell ability to produce macrocolonies on a solid nutrient medium. Genetic instability was defined by the delayed appearance of clones by cells surviving irradiation. Results: The delayed appearance of clones by cells surviving after irradiation has been well expressed and reached about 100% for diploid strain and only 20–25% for haploid strain independently of radiation type. Both cell survival and genetic instability exhibited more pronounced manifestation after the action of alpha particles than after irradiation with gamma-rays. This effect may be associated with greater efficiency of densely ionizing radiation to produce lethal radiation damage and accompanying sub-lesions responsible for delayed appearance of clones. The dependence of this effect on cell survival was substantially the same after exposure to UV light, sparsely and densely ionizing radiation. Conclusion: The genetic instability is mainly determined by cell ploidy rather than the shape of survival curve and the ability of cell to recover from radiation damage as it is traditionally assumed for Saccharomyces cerevisiae yeast cells.

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Radiosensitizers and radioprotectors are the compounds that modify the radiation therapy treatment. Radiosensitizers make tumor cell more sensitive to radiation therapy which increases the effectiveness of cancer treatment, whereas radioprotectors are the compounds that reduce the damage/spare normal tissue. Several of these compounds have been studied using appropriate biological model system and their efficacy is reported in literature. The main objectives of the bioinformatics database is to bring on single platform for researchers and clinicians. Therefore, we have developed bioinformatics database of radiosensitizers and radioprotectors using information available in PubMed, scientific journals, and other scientific sources. The collected information of these compounds systematically organized on single platform where a user can browse typical information of the compound. The information pertaining to these compounds is mainly on structural features, radiobiological aspects, biological targets, clinical trials, pharmacological aspects, toxicity, etc. Hence, the database would help clinicians, researchers, and scientists for the improvement of radiation therapy treatment.

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