Lectins of Sambucus nigra in Regulation of Cellular DNA-Protective Mechanisms

Genomes of living organisms are constantly affected by exogenous and endogenous factors, which lead to generating cytotoxic, carcinogenic and/or mutagenic DNA lesions. However, cells possess a number of DNA protective mechanisms. The repair enzyme, O-6-methylguanine-DNA methyltransferase (MGMT), plays a key role in the repair of primary DNA damage caused by alkylating compounds, which are widely used in industry and medicine. In humans, MGMT protects not only the integrity of the normal cell genome, but also contributes to the resistance of tumors to DNA-alkylating chemotherapeutic agents. Therefore, modulation of MGMT expression is a possible strategy to improve the efficiency of cancer therapy and to defend normal cells from toxicity of alkylating drugs. Various factors and compounds have been shown to influence the expression of the MGMT gene. Development of medicinal plants for this purpose is highly desirable, due to their safety, low toxicity, and ease of oral intake. The aim of our work was to study the potential of elderberry (Sambucus nigra) biologically active compounds of pharmacological interest, such as lectins, in modulating DNA damage repair process; in particular, the expression of the DNA repair enzyme MGMT. Lectins, ubiquitous in living organisms, are carbohydrate-recognizing proteins with a regulatory function. In elderberry lectins were found in roots, leaves, bark, fruits, seeds, flowers and pollen. Lectins can regulate the activity of different enzymes. We have investigated the modulating effect of S. nigra lectins on MGMT gene expression in mammalian cell cultures. These lectins were shown to be able to affect the genotoxic activity of the damaging agent nickel chloride, and to modulate in a concentration-dependent manner the MGMT gene expression at the protein level. Our results suggest that one of the protective mechanisms of the lectin action is stimulating DNA repair in a cell, including direct reversal repair with the help of MGMT enzyme.