Document Type : Original Article(s)
Authors
- Ramak Ajideh 1
- Elnaz Faghfuri 2
- Mina Hosseini 1
- Mohammad Hossein Yazdi 3
- Rouhollah Mirjani 4
- Zargham Sepehrizadeh 5
- Ahmad Reza Shahverdi 5
1 Biotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
2 Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
3 Recombinant Vaccine Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Genetics and Advanced Medical Technology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran
5 Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Background: Tellurium- containing compounds are suggested as the treatment agents for different diseases. This study aimed to synthesize tellurium nanoparticles (TeNPs) and study their in vitro and in vivo effects on tumour cells.
Method: In this experimental study, the synthesis of TeNPs in an aqueous solution was achieved with lactose as a reducing agent. The cells (2×104) were seeded, in triplicate, in 96-well plates and exposed to different concentrations of TeNPs for 48 hours. The determination of cell viability was done by MTT assay. In vivo studies were performed using breast cancer-bearing mice treated with TeNPs at different doses via intraperitoneal (IP) and intravenous (IV) injections.
Results: After 48 hours of treatment with TeNPs at different concentrations, cancer cell line viability was significantly decreased compared with control at almost all concentrations. Moreover, the IC50 of TeNPs in the non-cancerous cell line CHO (50.53 μg/mL) was far above that of EJ138 (29.60 μg/mL) and 4T1 (7.41 μg/mL) cell lines, revealing their lower toxicity in normal cells in comparison with cancer cells. The in vivo study's findings also showed that both delivery methods significantly inhibited tumor development, and that breast cancer-bearing mice lived longer than control mice, particularly when the largest dosage (400 μg, injected three times a week) was used.
Conclusion: These results demonstrate TeNPs as promising therapeutic agents for cancer treatment. However, further investigation is still needed to determine the in vitro and in vivo anticancer mechanisms of TeNPs.
Keywords
How to cite this article:
Ajideh R, Faghfuri E, Hosseini M, Yazdi MH, Mirjani R, Sepehrizadeh Z, et al. The cytotoxicity of tellurium nanoparticles on different cell lines and their in vivo anticancer effects in an animal model. Middle East J Cancer. 2023; 14(1):17-27. doi: 10. 30476/ mejc.2022.91698.1630.
- Sredni B. Immunomodulating tellurium compounds as anti-cancer agents. Semin Cancer Biol. 2012;22(1):60-9. doi: 10.1016/j.semcancer.2011.12. 003.
- Seng HL, Tiekink ERT. Anti-cancer potential of selenium- and tellurium-containing species: opportunities abound! Appl Organometal Chem. 2012;26(12):655-62. doi:10.1002/aoc.2928.
- Vávrová S, Struhárňanská E, Turňa J, Stuchlík S. Tellurium: A rare element with influence on prokaryotic and eukaryotic biological systems. Int J Mol Sci. 2021;22(11):5924. doi: 10.3390/ijms22115924.
- Fleming A, Young MY. The inhibitory action of potassium tellurite on coliform bacteria. J Pathol Bacteriol. 1940;51(1):29-35. doi: 10.1002/path. 1700510106.
- Cunha RL, Gouvea IE, Juliano L. A glimpse on biological activities of tellurium compounds. An Acad Bras Ciênc. 2009;81(3):393-407. doi: 10.1590/s0001- 37652009000300006.
- Nyska A, Waner T, Pirak M, Albeck M, Sredni B. Toxicity study in rats of a tellurium based immunomodulating drug, AS-101: a potential drug for AIDS and cancer patients. Arch Toxicol. 1989;63(5):386-93. doi: 10.1007/bf00303128.
- Okun E, Dikshtein Y, Carmely A, Saida H, Frei G, Sela BA, et al. The organotellurium compound ammonium trichloro(dioxoethylene-o,o')tellurate reacts with homocysteine to form homocystine and decreases homocysteine levels in hyperhomocysteinemic mice. FEBS J. 2007;274(12):3159-70. doi: 10.1111/j.1742- 4658.2007.05842.x.
- Sredni B, Geffen-Aricha R, Duan W, Albeck M, Shalit F, Lander HM, et al. Multifunctional tellurium molecule protects and restores dopaminergic neurons in Parkinson's disease models. FASEB J. 2007;21(8):1870- 83. doi: 10.1096/fj.06-7500com.
- Widy-Tyszkiewicz E, Piechal A, Gajkowska B, Smiałek M. Tellurium-induced cognitive deficits in rats are related to neuropathological changes in the central nervous system. Toxicol Lett. 2002;131(3):203-14. doi: 10.1016/s0378-4274(02)00050-4.
- Smiałek M, Gajkowska B, Otrebska D. Electron microscopy studies on the neurotoxic effect of sodium tellurite in the central nervous system of the adult rat. J Hirnforsch. 1994;35(2):223-32.
- Arakelova E. In vitro and in vivo anticancer activity of nanosize zinc oxide composites of doxorubicin. World Acad Sci Eng Technol. 2014;8(1):33-8. doi: doi.org/10.5281/zenodo.1336921.
- He Z, Yang Y, Liu JW, Yu SH. Emerging tellurium nanostructures: controllable synthesis and their applications. Chem Soc Rev. 2017;46(10):2732-53. doi: 10.1039/c7cs00013h.
- Li Y, Pan J, Jiang K, Zhou Y, Huang J, Ye J, et al. Preparation of elemental tellurium nanoparticles - Sucrose sol and its antioxidant activity in vitro. J Wuhan Univ Technol Mater Sci Ed. 2013;28:1048- 52. doi: 10.1007/s11595-013-0817-z.
- Tveden-Nyborg P, Bergmann TK, Jessen N, Simonsen U, Lykkesfeldt J. BCPT policy for experimental and clinical studies. Basic Clin Pharmacol Toxicol. 2021;128(1):4-8. doi: 10.1111/bcpt.13492.
- Mirjani R, Setayesh N, Faramarzi MA, Sharifzadeh M, Khoshayand M, Zare B, et al. Green synthesis, characterization, and biological evaluation of hydroxylcapped tellurium nanoparticles. J Sci I R Iran. 2021;32(4):321-30. doi: 10.22059/jsciences.2021. 321284.1007641.
- Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res. 1987;47(4):936- 42.
- Montero AJ, Jassem J. Cellular redox pathways as a therapeutic target in the treatment of cancer. Drugs. 2011;71(11):1385-96. doi: 10.2165/11592590- 000000000-00000.
- Sandoval JM, Verrax J, Vásquez CC, Calderon PB. A comparative study of tellurite toxicity in normal and cancer cells. Mol Cell Toxicol. 2012;8(4):327-34. doi: 10.1007/s13273-012-0040-6.
- Reinoso CA, Auger C, Appanna VD, Vásquez CC. Tellurite-exposed Escherichia coli exhibits increased intracellular α-ketoglutarate. Biochem Biophys Res Commun. 2012;421(4):721-6. doi: 10.1016/j.bbrc.2012.04.069.
- Zhang XD, Wu HY, Wu D, Wang YY, Chang JH, Zhai ZB, et al. Toxicologic effects of gold nanoparticles in vivo by different administration routes. Int J Nanomed. 2010;5:771-81. doi: 10.2147/ijn.s8428.
- Huang W, Wu H, Li X, Chen T. Facile one-pot synthesis of tellurium nanorods as antioxidant and anticancer agents. Chem Asian J. 2016;11(16):2301-11. doi: 10.1002/asia.201600757.
- Faghfuri E, Yazdi MH, Mahdavi M, Sepehrizadeh Z, Faramarzi MA, Mavandadnejad F, et al. Dose-response relationship study of selenium nanoparticles as an immunostimulatory agent in cancer-bearing mice. Arch Med Res. 2015;46(1):31-7. doi: 10.1016/j.arcmed. 2015.01.002.
- Caracelli I, Vega-Teijido M, Zukerman-Schpector J, Cezari MHS, Lopes JGS, Juliano L, et al. A telluriumbased cathepsin B inhibitor: Molecular structure, modelling, molecular docking and biological evaluation. J Mol Struct. 2012;1013:11-8. doi: doi:10.1016/j.molstruc.2012.01.008.
- Sredni B, Tichler T, Shani A, Catane R, Kaufman B, Strassmann G, et al. Predominance of TH1 response in tumor-bearing mice and cancer patients treated with AS 101. J Natl Cancer Inst. 1996;88(18):1276-84. doi: 10.1093/jnci/88.18.1276.
- Guest I, Uetrecht J. Bone marrow stem cell protection from chemotherapy by low--molecular-weight compounds. Exp Hematol. 2001;29(2):123-37. doi: 10.1016/s0301-472x(00)00621-4.
- Brodsky M, Yosef S, Galit R, Albeck M, Longo DL, Albeck A, et al. The synthetic tellurium compound, AS101, is a novel inhibitor of IL-1beta converting enzyme. J Interferon Cytokine Res. 2007;27(6):453- 62. doi: 10.1089/jir.2007.0168.
- Espinosa-Ortiz EJ, Rene ER, Guyot F, van Hullebusch ED, Lens PNL. Biomineralization of tellurium and selenium-tellurium nanoparticles by the white-rot fungus Phanerochaete chrysosporium. Internat Biodeterior Biodegradation. 2017;124:258-66. doi: doi:10.1016/j.ibiod.2017.05.009.
- Najimi S, Shakibaie M, Jafari E, Ameri A, Rahimi N, Forootanfar H, et al. Acute and subacute toxicities of biogenic tellurium nanorods in mice. Regul Toxicol Pharmacol. 2017;90:222-30. doi: 10.1016/j.yrtph. 2017.09.014.
- Khan A, Rashid A, Younas R, Chong R. A chemical reduction approach to the synthesis of copper nanoparticles. Int Nano Lett. 2016;6(1):21-6. doi: 10.1007/s40089-015-0163-6.
)