Regulation of Human DNA Primase-Polymerase PrimPol
AbstractTransmission of genetic information depends on successful completion of DNA replication. Genomic DNA is subjected to damage on a daily basis. DNA lesions create obstacles for DNA polymerases and can lead to the replication blockage, formation of DNA breaks, cell cycle arrest, and apoptosis. Cells have evolutionary adapted to DNA damage by developing mechanisms allowing elimination of lesions prior to DNA replication (DNA repair) and helping to bypass lesions during DNA synthesis (DNA damage tolerance). The second group of mechanisms includes the restart of DNA synthesis at the sites of DNA damage by DNA primase-pol...
Source: Biochemistry (Moscow) - August 1, 2023 Category: Biochemistry Source Type: research
Biochemical Mechanisms of Beneficial Effects of Beta-Alanine Supplements on Cognition
AbstractUsing nutritional interventions to cure and manage psychiatric disorders is a promising tool. In this regard, accumulating documents support strong relationships between the diet and brain health throughout the lifespan. Evidence from animal and human studies demonstrated that β-alanine (Beta-alanine; BA), a natural amino acid, provides several benefits in fight against cognitive decline promoting mental health. This review summarizes and reports state-of-the-art evidence on how BA affects cognitive health and argues existence of potential unrevealed biochemical mechanis ms and signaling cascades. There is a growi...
Source: Biochemistry (Moscow) - August 1, 2023 Category: Biochemistry Source Type: research
Mechanisms of Secondary Leukemia Development Caused by Treatment with DNA Topoisomerase Inhibitors
AbstractLeukemia is a blood cancer originating in the blood and bone marrow. Therapy-related leukemia is associated with prior chemotherapy. Although cancer therapy with DNA topoisomerase II inhibitors is one of the most effective cancer treatments, its side effects include development of secondary leukemia characterized by the chromosomal rearrangements affectingAML1 orMLL genes. Recurrent chromosomal translocations in the therapy-related leukemia differ from chromosomal rearrangements associated with other neoplasias. Here, we reviewed the factors that drive chromosomal translocations induced by cancer treatment with D...
Source: Biochemistry (Moscow) - July 1, 2023 Category: Biochemistry Source Type: research
Fluorescent Conjugates Based on Prostate-Specific Membrane Antigen Ligands as an Effective Visualization Tool for Prostate Cancer
AbstractFluorescent dyes are widely used in histological studies and in intraoperative imaging, including surgical treatment of prostate cancer (PC), which is one of the most common types of cancerous tumors among men today. Targeted delivery of fluorescent conjugates greatly improves diagnostic efficiency and allows for timely correct diagnosis. In the case of PC, the protein marker is a prostate-specific membrane antigen (PSMA). To date, a large number of diagnostic conjugates targeting PSMA have been created based on modified urea. The review focuses on the conjugates selectively binding to PSMA and answers the followin...
Source: Biochemistry (Moscow) - July 1, 2023 Category: Biochemistry Source Type: research
The Effect of Cell-Free DNA from Blood Serum of Mice with Metastatic Melanoma on Enhancement of Oncogenic Properties of Melanoma Cells
AbstractCurrently, a significant increase in the levels of circulating cell-free DNA (cfDNA) in the blood of patients is considered as a generally recognized marker of the development of oncological diseases. Although the tumor-associated cfDNA has been well studied, its biological functions remain unclear. In this work, we investigated the effect of cfDNA isolated from the blood serum of the mice with B16-F10 metastatic melanoma on the properties of the B16-F10 melanoma cellsin vitro. It was found that the profile of cfDNA isolated from the blood serum of mice with melanoma differs significantly from the cfDNA isolated ...
Source: Biochemistry (Moscow) - July 1, 2023 Category: Biochemistry Source Type: research
Histone Methyltransferases as a New Target for Epigenetic Action of Vorinostat
AbstractEpigenetic genome regulation during malignant cell transformation is characterized by the aberrant methylation and acetylation of histones. Vorinostat (SAHA) is an epigenetic modulator actively used in clinical oncology. The antitumor activity of vorinostat is commonly believed to be associated with the inhibition of histone deacetylases, while the impact of this drug on histone methylation has been poorly studied. Using HeLa TI cells as a test system allowing evaluation of the effect of epigenetically active compounds from the expression of theGFP reporter gene and gene knockdown by small interfering RNAs, we show...
Source: Biochemistry (Moscow) - July 1, 2023 Category: Biochemistry Source Type: research
Hereditary Conditions Associated with Elevated Cancer Risk in Childhood
AbstractWidespread use of the next-generation sequencing (NGS) technologies revealed that a significant percentage of tumors in children develop as a part of monogenic hereditary diseases. Predisposition to the development of pediatric neoplasms is characteristic of a wide range of conditions including hereditary tumor syndromes, primary immunodeficiencies, RASopathies, and phakomatoses. The mechanisms of tumor molecular pathogenesis are diverse and include disturbances in signaling cascades, defects in DNA repair, chromatin remodeling, and microRNA processing. Timely diagnosis of tumor-associated syndromes is important fo...
Source: Biochemistry (Moscow) - July 1, 2023 Category: Biochemistry Source Type: research
Targeting Methionine Addiction of Cancer Cells with Methioninase
AbstractAll types of cancer cells are addicted to methionine, which is known as the Hoffman effect. Restricting methionine inhibits the growth and proliferation of all tested types of cancer cells, leaving normal cells unaffected. Targeting methionine addiction with methioninase (METase), either alone or in combination with common cancer chemotherapy drugs, has been shown as an effective and safe therapy in various types of cancer cells and animal cancer models. About six years ago, recombinant METase (rMETase) was found to be able to be taken orally as a supplement, resulting in anecdotal positive results in patients with...
Source: Biochemistry (Moscow) - July 1, 2023 Category: Biochemistry Source Type: research
Evaluation of the Antitumor Potential of Soloxolone Tryptamide against Glioblastoma Multiforme Using in silico, in vitro, and in vivo Approaches
AbstractGlioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by uncontrollable diffusive growth, resistance to chemo- and radiotherapy, and a high recurrence rate leading to a low survival rate of patients with GBM. Due to a large number of signaling pathways regulating GBM pathogenesis, one of the promising directions is development of novel anti-glioblastoma compounds based on natural metabolites capable of affecting multiple targets. Here, we investigated the antitumor potential of the semisynthetic triterpenoid soloxolone tryptamide (STA) against human glioblastoma U87 cells. STA efficiently b...
Source: Biochemistry (Moscow) - July 1, 2023 Category: Biochemistry Source Type: research
Molecular Mechanisms of Tumor Cell Stemness Modulation during Formation of Spheroids
AbstractCancer stem cells (CSCs), their properties and interaction with microenvironment are of interest in modern medicine and biology. There are many studies on the emergence of CSCs and their involvement in tumor pathogenesis. The most important property inherent to CSCs is their stemness. Stemness combines ability of the cell to maintain its pluripotency, give rise to differentiated cells, and interact with environment to maintain a balance between dormancy, proliferation, and regeneration. While adult stem cells exhibit these properties by participating in tissue homeostasis, CSCs behave as their malignant equivalents...
Source: Biochemistry (Moscow) - July 1, 2023 Category: Biochemistry Source Type: research
Expression, Intracellular Localization, and Maturation of Cysteine Cathepsins in Renal Embryonic and Cancer Cell Lines
AbstractCysteine cathepsins play an important role in tumor development and metastasis. The expression of these enzymes is often increased in many types of tumor cells. Cysteine cathepsins contribute to carcinogenesis through a number of mechanisms, including proteolysis of extracellular matrix and signaling molecules on the cell surface, as well as degradation of transcription factors and disruption of signaling cascades in the cell nucleus. Distinct oncogenic functions have been reported for several members of the cysteine cathepsin family in various types of cancer, but a comparative study of all eleven cysteine catheps...
Source: Biochemistry (Moscow) - July 1, 2023 Category: Biochemistry Source Type: research
Molecular Ensembles of Microbiotic Metabolites in Carcinogenesis
AbstractThe mechanisms of carcinogenesis are extremely complex and involve multiple components that contribute to the malignant cell transformation, tumor growth, and metastasis. In recent decades, there has been a growing interest in the role of symbiotic human microbiota in the regulation of metabolism and functioning of host immune system. The symbiosis between a macroorganism and its microbiota has given rise to the concept of a holoorganism. Interactions between the components of a holoorganism have formed in the process of coevolution, resulting in the acquisition by microbiotic metabolites of a special role of signa...
Source: Biochemistry (Moscow) - July 1, 2023 Category: Biochemistry Source Type: research
S ‑Glutathionylation and S‑Nitrosylation as Modulators of Redox-Dependent Processes in Cancer Cell
AbstractDevelopment of oxidative/nitrosative stress associated with the activation of oncogenic pathways results from the increase in the generation of reactive oxygen and nitrogen species (ROS/RNS) in tumor cells, where they can have a dual effect. At high concentrations, ROS/RNS cause cell death and limit tumor growth at certain phases of its development, while their low amounts promote oxidative/nitrosative modifications of key redox-dependent residues in regulatory proteins. The reversibility of such modifications as S ‑glutathionylation and S‑nitrosylation that proceed through the electrophilic attack of ROS/RNS o...
Source: Biochemistry (Moscow) - July 1, 2023 Category: Biochemistry Source Type: research
Protein –Protein Interfaces as Druggable Targets: A Common Motif of the Pyridoxal-5′-Phosphate-Dependent Enzymes to Receive the Coenzyme from Its Producers
AbstractPyridoxal-5 ′-phosphate (PLP), a phosphorylated form of vitamin B6, acts as a coenzyme for numerous reactions, including those changed in cancer and/or associated with the disease prognosis. Since highly reactive PLP can modify cellular proteins, it is hypothesized to be directly transferred from its donors t o acceptors. Our goal is to validate the hypothesis by finding common motif(s) in the multitude of PLP-dependent enzymes for binding the limited number of PLP donors, namely pyridoxal kinase (PdxK), pyridox(am)in-5′-phosphate oxidase (PNPO), and PLP-binding protein (PLPBP). Experimentally confirme d intera...
Source: Biochemistry (Moscow) - July 1, 2023 Category: Biochemistry Source Type: research
Sphingolipid Metabolism in Tumor Cells
AbstractSphingolipids are a diverse family of complex lipids typically composed of a sphingoid base bound to a fatty acid via amide bond. The metabolism of sphingolipids has long remained out of focus of biochemical studies. Recently, it has been attracting an increasing interest of researchers because of different and often multidirectional effects demonstrated by sphingolipids with a similar chemical structure. Sphingosine, ceramides (N-acylsphingosines), and their phosphorylated derivatives (sphingosine-1-phosphate and ceramide-1-phosphates) act as signaling molecules. Ceramides induce apoptosis and regulate stability o...
Source: Biochemistry (Moscow) - July 1, 2023 Category: Biochemistry Source Type: research
