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Information × Registration Number 0225U000967, (0122U200211) , R & D reports Title Double-acting anticancer drugs for circumvention of the acquired resistance of malignant cells to chemotherapy popup.stage_title Дослідження впливу структурних елементів у молекулі хінон-вмісних сполук на їхню здатність утворювати аддукти з клітинними тіолами та індукувати окислювально-відновні реакції у цитозолі злоякісних клітин Head Panchuk Rostyslav R., Доктор біологічних наук Registration Date 22-01-2025 Organization Institute of Cell Biology of the National Academy of Sciences of Ukraine popup.description1 The main aim of this study is to investigate the relationship between fluctuations in the production of reactive oxygen species and quantitative changes in thiol levels in drug-resistant tumor cells under the action of anticancer antibiotics of the landomycin family. This will allow to elucidate the molecular mechanisms underlying the innate ability of landomycins to overcome acquired resistance of tumor cells to chemotherapy. popup.description2  In the course of the work, it was shown for the first time that the presence of the terminal L-rhodynose residue in the oligosaccharide chain and the hydroxyl group at position 11 of the landomycin aglycone ensures their maximum ROS-inducing, and hence antitumor activity. A sharp increase in hydrogen peroxide production under the influence of landomycins leads to a rapid decrease in the cytosolic level of glutathione, which is used by the cell in the detoxification reaction 2GSH+H2O2-->GSSG+H2O. In low doses, this effect of landomycins is short-lived, as cells are able to compensate the loss of glutathione, while higher concentrations of these substances lead to rapid death of tumor cells. Circumvention of acquired cancer drug resistance to chemotherapy treatment with landomycins is accompanied by a significant and prolonged increase in the production of hydrogen peroxide and autofluorescence of these compounds at 450 nm. This indicates that in order to kill such cells, landomycins must first eliminate a certain substrate, the amount of which in the HL-60/adr and HL-60/vinc sublines is greater than in the original drug-sensitive HL-60 cell line. Using specific dyes that selectively bind to reduced glutathione (monochlorobromine), it was shown that this substrate can be low-molecular-weight thiols, which fluoresce when bound to landomycin. The results obtained in the course of the research demonstrate the importance of combining thiol-binding and ROS-inducing activities in the chemical structure of landomycins, which allows these antitumor antibiotics to successfully overcome the acquired resistance of tumor cells to chemotherapy, which is of great practical importance. Product Description popup.authors Kozak Yuliia S. Stasiuk Nataliia Ye. popup.nrat_date 2025-01-22 Close