Molecular Ensembles of Microbiotic Metabolites in Carcinogenesis.

The 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 signaling molecules and main regulators of molecular interactions in the holoorganism. As elements of signaling pathways in the host organism, bacterial metabolites have become essential participants in various physiological and pathological processes, including tumor growth. At the same time, signaling metabolites often exhibit multiple effects and impact both the functions of the host cells and metabolic activity and composition of the microbiome. This review discusses the role of microbiotic metabolites in the induction and prevention of malignant transformation of cells in the host organism and their impact on the efficacy of anticancer therapy, with special emphasis on the involvement of some components of the microbial metabolite molecular ensemble in the initiation and progression of tumor growth.

Moonlight functions of glycolytic enzymes in cancer.

Since an extensive genome research has started, basic principle "one gene-one protein-one function" was significantly revised. Many proteins with more than one function were identified and characterized as "moonlighting" proteins, which activity depend not only on structural peculiarities but also on compartmentation and metabolic environment. It turned out that "housekeeping" glycolytic enzymes show important moonlight functions such as control of development, proliferation, apoptosis, migration, regulation of transcription and cell signaling. Glycolytic enzymes emerged very early in evolution and because of the limited content of genomes, they could be used as ancient regulators for intercellular and intracellular communication. The multifunctionality of the constitutively expressed enzymes began to serve cancer cell survival and growth. In the present review we discuss some moonlight functions of glycolytic enzymes that important for malignant transformation and tumor growth.

Evolutionary View on Lactate-Dependent Mechanisms of Maintaining Cancer Cell Stemness and Reprimitivization.

The role of lactic acid (lactate) in cell metabolism has been significantly revised in recent decades. Initially, lactic acid was attributed to the role of a toxic end-product of metabolism, with its accumulation in the cell and extracellular space leading to acidosis, muscle pain, and other adverse effects. However, it has now become obvious that lactate is not only a universal fuel molecule and the main substrate for gluconeogenesis but also one of the most ancient metabolites, with a signaling function that has a wide range of regulatory activity. The Warburg effect, described 100 years ago (the intensification of glycolysis associated with high lactate production), which is characteristic of many malignant tumors, confirms the key role of lactate not only in physiological conditions but also in pathologies. The study of lactate's role in the malignant transformation becomes more relevant in the light of the "atavistic theory of carcinogenesis," which suggests that tumor cells return to a more primitive hereditary phenotype during microevolution. In this review, we attempt to summarize the accumulated knowledge about the functions of lactate in cell metabolism and its role in the process of carcinogenesis and to consider the possible evolutionary significance of the Warburg effect.

An Overview of Alkylresorcinols Biological Properties and Effects.

The investigation of alkylresorcinols has drawn an increasing interest recently. Alkylresorcinols (ARs) are natural chemical compounds synthesized by bacteria, fungi, sponges, and higher plants, possessing a lipophilic polyphenol structures and a myriad of biological properties. Human takes ARs as a component of a whole grain diet (from whole grain rye, wheat, and barley products), and thus, alkylresorcinols are frequently used as whole grain intake markers. Besides, ARs are considered as promising bioregulators of metabolic and immune processes, as well as adjuvant therapeutic agents for antimicrobial and anticancer treatment. In this review, we attempted to systematize the accumulated information concerning ARs origin, metabolism, biological properties, and their effect on human health.