- PII
- S0006302924060157-1
- DOI
- 10.31857/S0006302924060157
- Publication type
- Article
- Status
- Published
- Authors
- Volume/ Edition
- Volume 70 / Issue number 1
- Pages
- 129-136
- Abstract
- The effect of astaxanthin, diethyldithiocarbamate and their combined application on cell proliferation was studied on mouse neuroblastoma culture N1E-115 (clone C-1300). There is evidence for the anti-cancer effect of astaxanthin in various tumour cell types. Diethyldithiocarbamates are used as additional drugs in chemotherapy. The use of non-toxic drug complexes is a new strategy for the treatment of cancer. We have shown that the action of diethyldithiocarbamate and astaxanthin both separately and in combination causes inhibition of proliferation and induction of differentiation of mouse neuroblastoma N1E-115 cells. Based on the results of Western blot analysis it was revealed that the combination of the drugs increased the expression of CHOP protein (marker of endoplasmic reticulum) and proapoptotic protein Bax, decreased the expression of anti-apoptotic protein Bcl-2, which may indicate the start of apoptotic cascade. Meanwhile, application of diethyldithiocarbamate alone caused a decrease in both Bax and Bcl-2 levels, but had no effect on CHOP protein expression. Apparently, astaxanthin modifies the effect of diethyldithiocarbamate when used together.
- Keywords
- астаксантин диэтилдитиокарбамат натрия пролиферация дифференцировка продукция активных форм кислорода митохондриальный мембранный потенциал
- Date of publication
- 24.10.2025
- Year of publication
- 2025
- Number of purchasers
- 0
- Views
- 19
References
- 1. 1. Lee S. J., Bai S. K., Lee K. S., Namkoohg S., Namkoong S., Na H. J., Ha K. S., Han J. A., Yim S. V., Chang K., Kwon Y. G., Lee S. K., and Kim Y. M. Astaxanthin inhibits nitric oxide production and inflammatory gene expression by suppressing IκB kinase-dependent NF-κB activation. Mol. Cells, 16, 97–105 (2003). PMID: 14503852
- 2. 2. Ambati R. R., Phang S. M., Ravi S., and Aswathanarayana R. G. Astaxanthin: sources, extraction, stability, biological activities and its commercial applications—a review. Mar. Drugs, 12, 128–152 (2014). DOI: 10.3390/md12010128
- 3. 3. Galasso C., Orefice I., Pellone P., Cirino P., Miele R., Ianora A., Brunet C., and Sansone C.. On the neuroprotective role of astaxanthin: New perspectives? Mar. Drugs, 16 (8), 247 (2018). DOI: 10.3390/md16080247
- 4. 4. Che H., Li Q., Zhang T., Wang D., Yang L., Xu J., Yanagita T., Xue C., Chang Y., and Wang Y. Effects of astaxanthin and docosahexaenoic-acid-acylated astaxanthin on Alzheimer's disease in APP/PS1 double-transgenic mice. J. Agric. Food Chem., 66 (19), 4948–4957 (2018). DOI: 10.1021/acs.jafc.8b00988
- 5. 5. Grimmig B., Kim S. H., Nash K., Bickford P. C., and Douglas Shytle R. Neuroprotective mechanisms of astaxanthin: a potential therapeutic role in preserving cognitive function in age and neurodegeneration. Geroscience, 39 (1), 19–32 (2017). DOI: 10.1007/s11357-017-9958-x
- 6. 6. Matias A. C., Manieri T. M., Cipriano S. S., Carioni V. M., Nomura C. S., Machado C. M., and Cerchiaro G. Diethyldithiocarbamate induces apoptosis in neuroblastoma cells by raising the intracellular copper level, triggering cytochrome c release and caspase activation. Toxicol. In Vitro, 27 (1), 349−357 (2013). DOI: 10.1016/j.tiv.2012.08.017
- 7. 7. Nobel C. I., Kimland M., Lind B., Orrenius S., and Slater A. F. Dithiocarbamates induce apoptosis in thymocytes by raising the intracellular level of redox-active copper. J. Biol. Chem., 270 (44), 26202–26208 (1995). DOI: 10.1074/jbc.270.44.26202
- 8. 8. Liu C., Liu Z., Fang Y., Liao Z., Zhang Z., Yuan X., YuT., Yang Y., Xiong M., Zhang X., Zhang G., Meng L., and Zhang Z., Exposure to dithiocarbamate fungicide maneb in vitro and in vivo: Neuronal apoptosis and underlying mechanisms, Environ. Int., 171, 107696 (2023). DOI: 10.1016/j.envint.2022.107696
- 9. 9. Solovieva M., Shatalin Y., Fadeev R., Krestinina O., Baburina Y., Kruglov A., Kharechkina E., Kobyakova M., Rogachevsky V., Shishkova E., and Akatov A. V. Vitamin B12b enhances the cytotoxicity of diethyldithiocarbamate in a synergistic manner, inducing the paraptosis-like death of human larynx carcinoma cells. Biomolecules, 10 (1), 69 (2020). DOI: 10.3390/biom10010069
- 10. 10. Nishitoh H. CHOP is amultifunctional transcription factor in the ER stress response. J. Biochem., 151, 217–219 (2012). DOI: 10.1093/jb/mvr143
- 11. 11. Solovieva M. E., Shatalin Y. V., Solovyev V. V., Sazonov A. V., Kutyshenko V. P., and Akatov V. S. Hydroxycobalamin catalyzes the oxidation of diethyldithiocarbamate and increases its cytotoxicity independently of copper ions. Redox Biol., 20, 28–37 (2019). DOI: 10.1016/j.redox.2018.09.016
- 12. 12. Ali I., Wani W. A., Saleem K., and Hseih M.-F. Design and synthesis of thalidomide based dithiocarbamate Cu(II), Ni(II) and Ru(III) complexes as anticancer agents. Polyhedron, 56 (12), 134–143 (2013).
- 13. DOI: 10.1016/j.poly.2013.03.056
- 14. 13. Altaf M., Monim-Ul-Mehboob M., Kawde A. N., Corona G., Larcher R., Ogasawara M., Casagrande N., Celegato M., Borghese C., Siddik Z. H., Aldinucci D., and Isab A. A. New bipyridine gold(III) dithiocarbamate-containing complexes exerted a potent anticancer activity against cisplatin-resistant cancer cells independent of p53 status. Oncotarget, 8 (1), 490–505 (2017). DOI: 10.18632/oncotarget.13448
- 15. 14. Amano T., Richelson E., and Nirenberg M. Neurotransmitter synthesis by neuroblastoma clones (neuroblast differentiation-cell culture-choline acetyltransferase-acetylcholinesterase-tyrosine hydroxylase-axons-dendrites). Proc. Natl. Acad. Sci. USA, 69 (1), 258–263 (1972). DOI: 10.1073/pnas.69.1.258
- 16. 15. Мякишева С. Н., Бабурина Ю. Л. и Крестинина О. В. Астаксантин и карбоксиамид изохинолина снижают
- 17. пролиферацию клеток нейробластомы мыши N1Е-115 (клон С-1300) и запускают пути апоптоза. Современные проблемы науки и образования, 5 (2022).
- 18. 16. Giorgi C., Romagnoli A., Pinton P., and Rizzuto R. Ca2+ signaling, mitochondria and cell death. Curr. Mol. Med., 8 (2), 119–130 (2008). DOI: 10.2174/156652408783769571
- 19. 17. Kruman I., Guo Q., and Mattson M. P. Calcium and reactive oxygen species mediate staurosporine-induced mitochondrial dysfunction and apoptosis in PC12 cells. J. Neurosci. Res., 51 (3), 293–308 (1998). DOI: 10.1002/(SICI)1097-4547(19980201)51:393:: AID-JNR33.0.CO;2-B
- 20. 18. Maciel E. N., Vercesi A. E., and Castilho R. F. Oxidative stress in Ca2+-induced membrane permeability transition in brain mitochondria. J. Neurochem., 79 (6), 1237–1245 (2001). DOI: 10.1046/j.1471-4159.2001.00670.x
- 21. 19. Pinton P., Giorgi C., Siviero R., Zecchini E., and Rizzuto R. Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene, 27 (50), 6407–6418 (2008). DOI: 10.1038/onc.2008.308
- 22. 20. Batista A. P., da Silva T. G., Teixeira Á. A., de Medeiros P. L., Teixeira V. W., Alves L. C., and dos Santos F. A. Melatonin effect on the ultrastructure of Ehrlich ascites tumor cells, lifetime and histopathology in Swiss mice. Life Sci., 93 (23), 882–888 (2013). PMID: 24383083
- 23. 21. Batista A. P., da Silva T. G., Teixeira A. A., de Medeiros P. L., Teixeira V. W., Alves L. C., Dos Santos F. A., and Silva E. C. Ultrastructural aspects of melatonin cytotoxicity on Caco-2 cells in vitro. Micron, 59, 17–23 (2014). DOI: 10.1016/j.micron.2013.12.003
- 24. 22. Bejarano I., Espino J., Marchena A. M., Barriga C., Paredes S. D., Rodríguez A. B., and Pariente J. A. Melatonin enhances hydrogen peroxide-induced apoptosis in human promyelocytic leukaemia HL-60 cells. Mol. Cell Biochem., 353 (1–2), 167–176 (2011). DOI: 10.1007/s11010-011-0783-8
- 25. 23. Hardwick J. M. and Soane L. Multiple functions of Bcl-2 family proteins. Cold Spring Harb. Perspect. Biol., 5 (2), a008722 (2013). DOI: 10.1101/cshperspect.a008722
- 26. 24. Мякишева С. Н., Бабурина Ю. Л., Кобякова М. И., Крестинин Р. Р., Сотникова Л. Д. и Крестинина О. В. Совместное действие мелатонина и диэтилдитиокарбамата на клетки нейробластомы мыши N1Е-115 (клон С-1300). Биофизика, 68, (5), 973–981 (2023). DOI: 10.31857/S0006302923050186
