The Role of reactive Oxygen Species in the Implementation of the Anti-Tumor Effect of Nanocomplexes Based on GdEuVO4 Nanoparticles and Cholesterol
DOI:
https://doi.org/10.20535/ibb.2024.8.2.295581Keywords:
nanocomplexes, Ehrlich adenocarcinoma cells, reactive oxygen species, apoptosis, necrosis, vanadium compoundsAbstract
Background. An experimental study of the antitumor effect of nanocomplexes (NCs) consisting of GdYEuVO4 nanoparticles and cholesterol indicates their potential use in oncological practice. The mechanism of the antitumor effect of NCs may be associated with the formation of reactive oxygen species (ROS), leading to subsequent tumor cell death.
Objective. To study the pro-oxidant and antitumor properties of NCs consisting of GdYEuVO4 nanoparticles and cholesterol in an in vitro system.
Methods. Experiments were performed on Ehrlich ascites carcinoma (EAC) cells, which were introduced intraperitoneally into BALB/c mice. On the 7th day of EAC development, cells were isolated and treated with NCs for 3 hours in vitro. Untreated cells served as the control. The formation of intracellular ROS was quantified by flow cytometry using the Fluorometric Intracellular ROS Kit. The metabolic activity of EAC cells was assessed using the colorimetric MTT test. The number of cells undergoing apoptosis or necrosis was evaluated using flow cytometry and the FITC Annexin V Apoptosis Detection Kit I.
Results. Incubation of EAC cells with NCs resulted in more than a 3-fold increase in ROS formation compared to the control. NCs also caused almost a two-fold inhibition of the metabolic activity of EAC cells, accompanied by a 25% decrease in the number of viable EAC cells. It was shown that NCs are unique compounds capable of simultaneously inducing several types of cell death, with necrosis being the predominant mode of tumor cell death after NC treatment.
Conclusions. The cytotoxic effect of NCs on tumor cells is mediated through their pro-oxidant properties. These results can be considered when developing new cancer therapy strategies.
References
Zraik IM, Heß-Busch Y. Management von Nebenwirkungen der Chemotherapie und deren Langzeitfolgen [Management of chemotherapy side effects and their long-term sequelae]. Urologe A. 2021 Jul; 60(7):862-71. DOI: 10.1007/s00120-021-01569-7
Xu X, Li T, Jin K. Bioinspired and biomimetic nanomedicines for targeted cancer therapy. Pharmaceutics. 2022 May;14(5):1109. DOI: 10.3390/pharmaceutics14051109
Kowalski S, Wyrzykowski D, Inkielewicz-Stepniak I. Molecular and cellular mechanisms of cytotoxic activity of vanadium compounds against cancer cells. Molecules. 2020;25(7):1757. DOI: 10.3390/molecules25071757
Goltsev AM, Dubrava TG, Gaevska YO, Babenko NM, Bondarovych MO, Lutsenko OD. Functional activity of animal bone marrow cells after their treatment with nanocomplexes. Ukr J Radiol Oncol. 2021;29(2):9-21. DOI: 10.46879/ukroj.2.2021.9-21
Crans DC, Yang L, Haase A, Yang X. Health benefits of vanadium and its potential as an anticancer agent. In: Sigel A, Sigel H, Freisinger E, Sigel RKO, editors. Metallo-Drugs: Development and Action of Anticancer Agents. De Gruyter; 2018. DOI: 10.1515/9783110470734-015
Klochkov VK, inventor; ISMA NAS of Ukraine, assignee. Method for producing water dispersion of cholesterol. Ukraine patent 108011. 2015 March 10.
Shen L, Zhang C, Cui K, Liang X, Zhu G. Low-density lipoprotein contributes to endometrial carcinoma cell proliferation, migration, and invasion by activating the JAK-STAT signaling pathway. Anal Cell Pathol (Amst). 2023 Oct; 2023:4015167. DOI: 10.1155/2023/4015167
Al-Jarallah A, Trigatti BL. A role for the scavenger receptor, class B type I in high density lipoprotein dependent activation of cellular signaling pathways. Biochim Biophys Acta. 2010;1801(12):1239-48. DOI: 10.1016/j.bbalip.2010.08.006
Goltsev AN, Babenko NN, Gaevskaya YA, Chelombitko OV, Bondarovich NA, Dubrava TG, et al. Functional activity of Ehrlich carcinoma cells after treatment with hybrid nanocomplexes containing orthovanadates of rare-earth elements, cholesterol and luminescent dye. Fiziol Zh. 2015;61(6):60-8. DOI: 10.15407/fz61.06.060
Goltsev AN, Babenko NN, Gaevskaya YA, Bondarovich NA, Dubrava TG, Ostankov MV, et al. Nanotechniques inactivate cancer stem cells. Nanoscale Res Lett. 2017 Dec;12(1):415. DOI: 10.1186/s11671-017-2175-9
Aureliano M, De Sousa-Coelho AL, Dolan CC, Roess DA, Crans DC. Biological consequences of vanadium effects on formation of reactive oxygen species and lipid peroxidation. Int J Mol Sci. 2023 Mar;24(6):5382. DOI: 10.3390/ijms24065382
Ścibior A, Kurus J. Vanadium and oxidative stress markers - in vivo model: a review. Curr Med Chem. 2019;26(29):5456-500. DOI: 10.2174/0929867326666190108112255
Kumar S, Kumari S, Karan R, Kumar A, Rawal RK, Gupta PK. Anticancer perspectives of vanadium complexes. Inorganic Chemistry Communications. 2024;161:112014. DOI: 10.1016/j.inoche.2023.112014
Raimondi V, Ciccarese F, Ciminale V. Oncogenic pathways and the electron transport chain: a dangeROS liaison. Br J Cancer. 2020 Jan;122(2):168-81. DOI: 10.1038/s41416-019-0651-y
Yefimova SL, Maksimchuk PO, Hubenko KO, Omielaieva VV, Kavok NS, Klochkov VK, et al. Light-triggered redox activity of GdYVO4:Eu3+ nanoparticles. Spectrochim Acta A Mol Biomol Spectrosc. 2020 Dec;242:118741. DOI: 10.1016/j.saa.2020.118741
Goltsev A, Babenko N, Gaevska Y, Bondarovych M, Dubrava T, Ostankova L, et al. Toxicity of nanocomplexes containing gadolinium orthovanadate nanoparticles and cholesterol. Biol Trace Elem Res. 2022;200(10):4339-54. DOI: 10.1007/s12011-021-03019-z
Goltsev AM, Malyukin YV, Babenko NM, Gaevska YO, Bondarovych MO, Dubrava TG, et al. Antitumor activity of spherical nanoparticles GdYVO4: Eu3+ depends on pre-incubation time. Appl Nanosci (Switzerland). 2020;10(8):2749-58. DOI: 10.1007/s13204-020-01284-3
Klochkov VK. Aqueous colloid solutions of nanoluminophores nReVO4:Eu3+ (Re = Y, Gd, La). Mater Sci Nanostruct. 2009;2:3-8.
Ehrlich P, Apolant H. Beobachtungen Über Maligne Mausen tumoren. Berlin Klin Wschr. 1905;28:871-4.
Ozaslan M, Karagos ID, Kilic IH, Guldur ME. Erlich ascites carcinoma. Afr J Biotechnol. 2011;10:2375-8.
Korbecki J, Baranowska-Bosiacka I, Gutowska I, Chlubek D. Biochemical and medical importance of vanadium compounds. Acta Biochim Pol. 2012;59(2):195-200. DOI: 10.18388/abp.2012_2138
Kruk J, Aboul-Enein HY. Reactive oxygen and nitrogen species in carcinogenesis: implications of oxidative stress on the progression and development of several cancer types. Mini Rev Med Chem. 2017;17(11):904-19. DOI: 10.2174/1389557517666170228115324
Moskalenko AM, Lukyanchuk OV, Badiuk NS, Vasiuk VL, Gozhenko AI. Oxidative stress at tumors. Visnyk Morskoi Medytsyny. 2019;4(85):134-42.
Mittler R. Oxidative stress, antioxidants and stress tolerance. Trends Plant Sci. 2002 Sep;7(9):405-10. DOI: 10.1016/s1360-1385(02)02312-9
Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012 May;24(5):981-90. DOI: 10.1016/j.cellsig.2012.01.008
Xiaogai Y. Vanadium compounds induce stronger growth suppression in PTEN-deficient prostate cancer cells by ROS-mediated mechanism. J Chin Pharmaceut Sci. 2017;26(6):432-9. DOI: 10.5246/jcps.2017.06.047
Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, et al. ROS in cancer therapy: the bright side of the moon. Exp Mol Med. 2020 Feb;52(2):192-203. DOI: 10.1038/s12276-020-0384-2
Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov. 2009;8(7):579-91. DOI: 10.1038/nrd2803
Luo M, Zhou L, Huang Z, Li B, Nice EC, Xu J, et al. Antioxidant therapy in cancer: Rationale and progress. Antioxidants (Basel). 2022 Jun;11(6):1128. DOI: 10.3390/antiox11061128
Harris IS, DeNicola GM. The Complex Interplay between Antioxidants and ROS in Cancer. Trends Cell Biol. 2020;30(6):440-51. DOI: 10.1016/j.tcb.2020.03.002
Hwang HJ, Hong SH, Moon HS, Yoon YE, Park SY. Ginsenoside Rh2 sensitizes the anti-cancer effects of sunitinib by inducing cell cycle arrest in renal cell carcinoma. Sci Rep. 2022 Nov;12(1):19752. DOI: 10.1038/s41598-022-20075-0
Leventic M, Opacak-Bernardi T, Rastija V, Matic J, Pavlovic Saftic D, Ban Z, et al. The mechanism of anti-tumor activity of 6-morpholino- and 6-amino-9-sulfonylpurine derivatives on human leukemia cells. Molecules. 2023 Aug;28(16):6136. DOI: 10.3390/molecules28166136
Mehdad A, Brumana G, Souza AA, Barbosa J, Ventura MM, de Freitas SM. A Bowman-Birk inhibitor induces apoptosis in human breast adenocarcinoma through mitochondrial impairment and oxidative damage following proteasome 20S inhibition. Cell Death Discov. 2016 Mar;2(1):15067. DOI: 10.1038/cddiscovery.2015.67
Wu JX, Hong YH, Yang XG. Bis(acetylacetonato)-oxidovanadium(IV) and sodium metavanadate inhibit cell proliferation via ROS-induced sustained MAPK/ERK activation but with elevated AKT activity in human pancreatic cancer AsPC-1 cells. J Biol Inorg Chem. 2016 Dec;21(8):919-29. DOI: 10.1007/s00775-016-1389-0
Premanathan M, Karthikeyan K, Jeyasubramanian K, Manivannan G. Selective toxicity of ZnO nanoparticles toward Gram-positive bacteria and cancer cells by apoptosis through lipid peroxidation. Nanomedicine. 2011 Apr;7(2):184-92. DOI: 10.1016/j.nano.2010.10.001
Gurunathan S, Han JW, Eppakayala V, Jeyaraj M, Kim JH. Cytotoxicity of biologically synthesized silver nanoparticles in MDA-MB-231 human breast cancer cells. Biomed Res Int. 2013;2013:535796. DOI: 10.1155/2013/535796
Fleury C, Mignotte B, Vayssière JL. Mitochondrial reactive oxygen species in cell death signaling. Biochimie. 2002 Feb-Mar;84(2-3):131-41. DOI: 10.1016/s0300-9084(02)01369-x
Indran IR, Tufo G, Pervaiz S, Brenner C. Recent advances in apoptosis, mitochondria and drug resistance in cancer cells. Biochim Biophys Acta. 2011 Jun;1807(6):735-45. DOI: 10.1016/j.bbabio.2011.03.010
Liu M, Gu X, Zhang K, Ding Y, Wei X, Zhang X, et al. Gold nanoparticles trigger apoptosis and necrosis in lung cancer cells with low intracellular glutathione. J Nanopart Res. 2013;15(8):1745. DOI: 10.1007/s11051-013-1745-8
Phuc LTM, Taniguchi A. Polystyrene nanoparticles induce apoptosis or necrosis with or without epidermal growth factor. J Nanosci Nanotechnol. 2019 Aug;19(8):4812-7. DOI: 10.1166/jnn.2019.16347
Myshunina TM, Kalinichenko OV, Tron'ko MD. Mechanism of apoptosis in the thyroid cells under thyroid pathology. Fiziologichnyi Zhurnal. 2009;55(6):90-102.
Sathianathen NJ, Krishna S, Anderson JK, Weight CJ, Gupta S, Konety BR, et al. The current status of immunobased therapies for metastatic renal-cell carcinoma. Immunotargets Ther. 2017 Dec;6:83-93. DOI: 10.2147/ITT.S134850
Luo JL, Kamata H, Karin M. IKK/NF-kappaB signaling: balancing life and death-a new approach to cancer therapy. J Clin Invest. 2005 Oct;115(10):2625-32. DOI: 10.1172/JCI26322
Nagata S, Tanaka M. Programmed cell death and the immune system. Nat Rev Immunol. 2017 May;17(5):333-40. DOI: 10.1038/nri.2016.153
Goltsev AN, Malyukin YV, Dubrava TG, Babenko NN, Gaevskaya YA, Chelombytko OV, et al. Nanocomposites specifically penetrate and inhibit tumor cells. Mat-wiss u Werkstofftech. 2016;47(2-3):156-64. DOI: 10.1002/mawe.201600457
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