CHANGES IN BIOENERGETIC CHARACTERISTICS OF THE MURINE LYMPHOMA CELLS UNDER THE ACTION OF A THIAZOLE DERIVATIVE IN COMPLEX WITH POLYMERIC NANOPARTICLES
DOI: http://dx.doi.org/10.30970/sbi.1803.787
Abstract
Background. Mitochondria can influence cancer cells both indirectly via reactive oxygen species mediation and directly through mitochondrial biogenesis. Energy production in mitochondria is crucial as it facilitates the synthesis of essential molecules needed for cellular biosynthesis, growth, and proliferation. The development of new anticancer drugs that target the energy metabolism of tumor cells shows promise in cancer treatment. Our study aimed to investigate how the thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1), the polymeric nanoparticles based on the polyethylene glycol (PEG-PN, Th5), and their complex with BF1 (Th6) affect respiration and mitochondrial membrane potential in murine NK/Ly tumor cells.
Materials and Methods. The study was performed on white wild-type male mice with grafted NK/Ly lymphoma. The test substances were added to the cell suspension at a final concentration of 10 μM and incubated for 15 min at 37 °C. Oxygen uptake rates in NK/Ly cells were measured using a polarographic method with Clark electrode. Changes in mitochondrial membrane potential were assessed using the tetramethylrhodamine methyl ester fluorescence dye. The fluorescence intensity was evaluated using the ImageJ computer program.
Results. After incubating NK/Ly cells with BF1 (10 µM), Th5, or the BF1 + PEG-PN complex (Th6) for 15 min, no changes were observed in glucose-fueled basal respiration. However, the Th6 complex significantly activated FCCP-stimulated respiratory processes in NK/Ly lymphoma cells. Fluorescent microscopy data indicated that BF1 or Th5 alone did not affect mitochondrial membrane potential values. However, the Th6 complex significantly decreased mitochondrial membrane potential, suggesting a reduction in NK/Ly cell viability.
Conclusions The investigated complex of thiazole derivative BF1 with PEG-based polymeric nanoparticles may realize its cytotoxic effect by depolarization of mitochondrial membrane in NK/Ly lymphoma cells.
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| Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 74(3), 229-263. doi:10.3322/caac.21834 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Chen, X., Li, L., Guan, Y., Yang, J., & Cheng, Y. (2016). Anticancer strategies based on the metabolic profile of tumor cells: therapeutic targeting of the Warburg effect. Acta Pharmacologica Sinica, 37(8), 1013-1019. doi:10.1038/aps.2016.47 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Cunha, A., Silva, P. M. A., Sarmento, B., & Queirós, O. (2023). Targeting glucose metabolism in cancer cells as an approach to overcoming drug resistance. Pharmaceutics, 15(11), 2610. doi:10.3390/pharmaceutics15112610 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Fadaka, A., Ajiboye, B., Ojo, O., Adewale, O., Olayide, I., & Emuowhochere, R. (2017). Biology of glucose metabolization in cancer cells. Journal of Oncological Sciences, 3(2), 45-51. doi:10.1016/j.jons.2017.06.002 Crossref ● Google Scholar | ||||
| ||||
| Fogg, V. C., Lanning, N. J., & MacKeigan, J. P. (2011). Mitochondria in cancer: at the crossroads of life and death. Chinese Journal of Cancer, 30(8), 526-539. doi:10.5732/cjc.011.10018 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Horbay, R. O., Manko, B. O., Manko, V. V., Lootsik, M. D., & Stoika, R. S. (2011). Respiration characteristics of mitochondria in parental and giant transformed cells of the murine Nemeth–Kellner lymphoma. Cell Biology International, 36(1), 71-77. doi:10.1042/cbi20110017 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Hreniukh, V. P., Finiuk, N. S., & Shalai, Ya. R. (2020). Effects of thiazole derivatives on intracellular structure and functions in murine lymphoma cells. The Ukrainian Biochemical Journal, 92(2), 121-130. doi:10.15407/ubj92.02.121 Crossref ● Google Scholar | ||||
| ||||
| Ilkiv, M. V., Shalai, Ya. R., Manko, B. O., Ostapiuk, Yu. V., Mitina, N. E., Zaichenko, A. S., & Babsky, A. M. (2022). Generation of ROS under the influence of thiazole derivative and its complexes with PEG-based polymeric nanoparticles. Biopolymers and Cell, 38(3), 158-168. doi:10.7124/bc.000a7d Crossref ● Google Scholar | ||||
| ||||
| Ilkiv, M. V., Shalai, Ya. R., Mazur, H. M., Manko, B. O., Manko, B. V., Ostapiuk, Yu. V., Mitina, N. E., Zaichenko, A. S., & Babsky, A. M. (2023). Bioenergetic characteristics of the murine Nemeth–Kellner lymphoma cells exposed to thiazole derivative in complex with polymeric nanoparticles. The Ukrainian Biochemical Journal, 94(6), 30-36. doi:10.15407/ubj94.06.030 Crossref ● Google Scholar | ||||
| ||||
| Kapur, A., Mehta, P., Simmons, A. D., Ericksen, S. S., Mehta, G., Palecek, S. P., Felder, M., Stenerson, Z., Nayak, A., Dominguez, J. M. A., Patankar, M., & Barroilhet, L. M. (2022). Atovaquone: an inhibitor of oxidative phosphorylation as studied in gynecologic cancers. Cancers, 14(9), 2297. doi:10.3390/cancers14092297 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Liu, Y., & Shi, Y. (2020). Mitochondria as a target in cancer treatment. MedComm, 1(2), 129-139. doi:10.1002/mco2.16 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Środa-Pomianek, K., Michalak, K., Świątek, P., Poła, A., Palko-Łabuz, A., & Wesołowska, O. (2018). Increased lipid peroxidation, apoptosis and selective cytotoxicity in colon cancer cell line LoVo and its doxorubicin-resistant subline LoVo/Dx in the presence of newly synthesized phenothiazine derivatives. Biomedicine & Pharmacotherapy, 106, 624-636. doi:10.1016/j.biopha.2018.06.170 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Torchilin, V. P. (2014). Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery. Nature Reviews. Drug Discovery, 13(11), 813-827. doi:10.1038/nrd4333 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Wan, Y., Long, J., Gao, H., & Tang, Z. (2021). 2-Aminothiazole: a privileged scaffold for the discovery of anti-cancer agents. European Journal of Medicinal Chemistry, 210, 112953. doi:10.1016/j.ejmech.2020.112953 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Winter, J. M., Yadav, T., & Rutter, J. (2022). Stressed to death: mitochondrial stress responses connect respiration and apoptosis in cancer. Molecular Cell, 82(18), 3321-3332. doi:10.1016/j.molcel.2022.07.012 Crossref ● PubMed ● PMC ● Google Scholar | ||||
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Copyright (c) 2024 Yaryna Shalai, Marta Ilkiv, Anna Salamovska, Halyna Mazur, Bohdan Manko, Yurii Ostapiuk, Nataliya Mitina, Oleksandr Zaichenko, Andriy Babsky
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