Cellular and DNA Toxicity Study of Triphenyltin Ethyl Phenyl Dithiocarbamate and Triphenyltin Butyl Phenyl Dithiocarbamate on K562, Leukemia Cell Line

  • Authors: Hamid A.1, Rajab N.F.2, Charmagne Y.3, Awang N.4, Jufri N.F.1, Rasli N.R.5
  • Affiliations:
    1. Program of Biomedical Science, Center for Toxicology and Health Risk Study, Faculty of Health Sciences, Universiti Kebangsaan Malaysia
    2. Program of Biomedical Science, Centre for Healthy Ageing and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia,
    3. Program of Biomedical Science, Center for Toxicology and Health Risk Study, Faculty of Health Sciences,, Universiti Kebangsaan Malaysia
    4. Program of Environmental Health & Industrial Safety, Center for Toxicology and Health Risk Study, Faculty of Health Sciences,, Universiti Kebangsaan Malaysia,
    5. rogram of Biomedical Science, Center for Toxicology and Health Risk Study, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz
  • Issue: Vol 24, No 1 (2024)
  • Pages: 58-65
  • Section: Oncology
  • URL: https://snv63.ru/1871-5206/article/view/643677
  • DOI: https://doi.org/10.2174/0118715206266851231025054446
  • ID: 643677

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Abstract

Introduction:Continuous research for new effective drugs to treat cancer has improved our understanding on the mechanism of action of these drugs and paved new potential for their application in cancer treatments. In this study, organotin compounds known as triphenyltin ethyl phenyl dithiocarbamate and triphenyltin butyl phenyl dithiocarbamate were investigated for their toxicity on leukemia cell line (K562) and non-cancerous cell line (Chang liver cell and lung fibroblast, V79 cell).

Methods:MTT assay was performed to evaluate the cytotoxic effects of both compounds toward the cells after 24, 48 and 72 hours of exposure or treatment. The alkaline comet assay was conducted to determine the DNA damage on K562 cells after been exposed to both compounds for 30, 60 and 90 minutes.

Results:The IC50 values obtained from K562 cells ranged from 0.01 to 0.30 µM, whereas for both Chang liver cell and lung fibroblast V79 cell, the values ranged from 0.10 to 0.40 µM. For genotoxicity evaluation, the percentage of damaged DNA is measured as an average of tail moment, and was found to be within 1.20 to 2.20 A.U while the percentage of DNA intensity ranging from 1.50 to 3.50% indicating no genotoxic effects.

Conclusion:Both compounds are cytotoxic toward leukemia cells and non-cancerous cells but do not exert their genotoxic effects towards leukemia cell.

About the authors

Asmah Hamid

Program of Biomedical Science, Center for Toxicology and Health Risk Study, Faculty of Health Sciences, Universiti Kebangsaan Malaysia

Author for correspondence.
Email: info@benthamscience.net

Nor Fadilah Rajab

Program of Biomedical Science, Centre for Healthy Ageing and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia,

Email: info@benthamscience.net

Yip Charmagne

Program of Biomedical Science, Center for Toxicology and Health Risk Study, Faculty of Health Sciences,, Universiti Kebangsaan Malaysia

Email: info@benthamscience.net

Normah Awang

Program of Environmental Health & Industrial Safety, Center for Toxicology and Health Risk Study, Faculty of Health Sciences,, Universiti Kebangsaan Malaysia,

Email: info@benthamscience.net

Nurul Farhana Jufri

Program of Biomedical Science, Center for Toxicology and Health Risk Study, Faculty of Health Sciences, Universiti Kebangsaan Malaysia

Email: info@benthamscience.net

Nur Rasyiqin Rasli

rogram of Biomedical Science, Center for Toxicology and Health Risk Study, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz

Email: info@benthamscience.net

References

  1. Zylbersztejn, F.; Flores-Violante, M.; Voeltzel, T.; Nicolini, F.E.; Lefort, S.; Maguer-Satta, V. The BMP pathway: A unique tool to decode the origin and progression of leukemia. Exp. Hematol., 2018, 61, 36-44. doi: 10.1016/j.exphem.2018.02.005 PMID: 29477370
  2. Kassahun, W.; Tesfaye, G.; Bimerew, LG.; Fufa, D.; Adissu, W.; Yemane, T. Prevalence of leukemia and associated factors among patients with abnormal hematological parameters in Jimma Medical Center, Southwest Ethiopia: A cross-sectional study. Adv. Hematol. 2020, 2020. doi: 10.1155/2020/2014152
  3. Loscocco, F.; Visani, G.; Galimberti, S.; Curti, A.; Isidori, A. BCR-ABL independent mechanisms of resistance in chronic myeloid leukemia. Front. Oncol., 2019, 9, 939. doi: 10.3389/fonc.2019.00939 PMID: 31612105
  4. Amarante-Mendes, G.P.; Rana, A.; Datoguia, T.S.; Hamerschlak, N.; Brumatti, G. BCR-ABL1 tyrosine kinase complex signaling transduction: challenges to overcome resistance in chronic myeloid leukemia. Pharmaceutics, 2022, 14(1), 215. doi: 10.3390/pharmaceutics14010215 PMID: 35057108
  5. Nickoloff, J.A. Targeting replication stress response pathways to enhance genotoxic chemo-and radiotherapy. Molecules, 2022, 27(15), 4736. doi: 10.3390/molecules27154736 PMID: 35897913
  6. Lang, F.; Liu, Y.; Chou, F.J.; Yang, C. Genotoxic therapy and resistance mechanism in gliomas. Pharmacol. Ther., 2021, 228, 107922. doi: 10.1016/j.pharmthera.2021.107922 PMID: 34171339
  7. Çiftçiler, R.; Haznedaroglu, I.C. Tailored tyrosine kinase inhibitor (TKI) treatment of chronic myeloid leukemia (CML) based on current evidence. Eur. Rev. Med. Pharmacol. Sci., 2021, 25(24), 7787-7798. PMID: 34982440
  8. García-Gutiérrez, V.; Breccia, M.; Jabbour, E.; Mauro, M.; Cortes, J.E. A clinician perspective on the treatment of chronic myeloid leukemia in the chronic phase. J. Hematol. Oncol., 2022, 15(1), 90. doi: 10.1186/s13045-022-01309-0 PMID: 35818053
  9. Genthon, A.; Nicolini, F.E.; Huguet, F.; Colin-Gil, C.; Berger, M.; Saugues, S.; Janel, A.; Hayette, S.; Cohny-Makhoul, P.; Cadoux, N.; Cayuela, J.M.; Campos, L.; Guyotat, D.; Flandrin-Gresta, P. Influence of major BCR-ABL1 transcript subtype on outcome in patients with chronic myeloid leukemia in chronic phase treated frontline with nilotinib. Oncotarget, 2020, 11(26), 2560-2570. doi: 10.18632/oncotarget.27652 PMID: 32655840
  10. Breccia, M.; Alimena, G. Second-generation tyrosine kinase inhibitors (TKI) as salvage therapy for resistant or intolerant patients to prior tkis. Mediterr. J. Hematol. Infect. Dis., 2014, 6(1), e2014003. doi: 10.4084/mjhid.2014.003 PMID: 24455112
  11. Mehri, A. Trace elements in human nutrition (II)–an update. Int. J. Prev. Med., 2020, 11, 2. PMID: 32042399
  12. Ovejero, P. K.; Díaz-García, D.; García-Almodóvar, V.; Lozano Chamizo, L.; Marciello, M.; Díaz-Sánchez, M.; Prashar, S.; Gómez-Ruiz, S.; Filice, M. Multifunctional silica-based nanoparticles with controlled release of organotin metallodrug for targeted theranosis of breast cancer. Cancers, 2020, 12(1), 187. doi: 10.3390/cancers12010187 PMID: 31940937
  13. Graisa, A.M.; Husain, A.A.; Al-Mashhadani, M.H.; Ahmed, D.S.; Adil, H.; Yousif, E. The organotin applications in biological, industrial and agricultural sectors: A systematic review. J. Serambi Eng., 2022, 7(1)
  14. Zhang, S.; Li, P.; Li, Z.H. Toxicity of organotin compounds and the ecological risk of organic tin with co-existing contaminants in aquatic organisms. Comp. Biochem. Physiol. C Toxicol. Pharmacol., 2021, 246, 109054. doi: 10.1016/j.cbpc.2021.109054 PMID: 33887478
  15. Chen, C.; Chen, L.; Xue, R.; Huang, Q.; Wu, L.; Ye, S.; Zhang, W. Spatiotemporal variation and source apportionment of organotin compounds in sediments in the Yangtze Estuary. Environ. Sci. Eur., 2019, 31, 1-9.
  16. Nur Adibah, M.A. Synthesis, characterization and encapsulation studies of multidentate ligands and their organotin complexes / Nur Adibah Mohd Amin.. Masters thesis, University of Malaya 2019.
  17. Arraq, R.R.; Hadi, A.G. Enhanced the antioxidant activity of tri organotin (IV) complexes derived from cephalexin. Azerbaijan Med. J. 2022, 2022.
  18. Ajiboye, T.O.; Ajiboye, T.T.; Marzouki, R.; Onwudiwe, D.C. The versatility in the applications of dithiocarbamates. Int. J. Mol. Sci., 2022, 23(3), 1317. doi: 10.3390/ijms23031317 PMID: 35163241
  19. Bansal, O. Health impacts of the carbamate and dithiocarbamate pesticides: A review. Int. J. Sci. Res. Publ., 2022, 12(2) doi: 10.29322/IJSRP.12.02.2022.p12250
  20. Abd Aziz, N.A.; Awang, N.; Chan, K.M.; Kamaludin, N.F.; Anuar, N.N.M. Organotin (IV) dithiocarbamate compounds as anticancer agents: A review of syntheses and cytotoxicity studies. Molecules, 2023, 28(15), 5841.
  21. Rasli, N.R.; Hamid, A.; Awang, N.; Kamaludin, N.F. Series of organotin(IV) compounds with different dithiocarbamate ligands induced cytotoxicity, apoptosis and cell cycle arrest on jurkat E6.1, T acute lymphoblastic leukemia cells. Molecules, 2023, 28(8), 3376. doi: 10.3390/molecules28083376 PMID: 37110610
  22. Sirajuddin, M.; Ali, S.; Tahir, M.N. Organotin(IV) derivatives based on 2-((2-methoxyphenyl)carbamoyl)benzoic acid: Synthesis, spectroscopic characterization, assessment of antibacterial, DNA interaction, anticancer and antileishmanial potentials. J. Mol. Struct., 2021, 1229, 129600. doi: 10.1016/j.molstruc.2020.129600
  23. Hamid, A.; Azmi, M.A.; Rajab, N.F.; Awang, N.; Jufri, N.F. Cytotoxic effects of organotin(IV) dithiocarbamate compounds with different functional groups on leukemic cell line, K-562. Sains Malays., 2020, 49(6), 1421-1430. doi: 10.17576/jsm-2020-4906-20
  24. Devi, J.; Boora, A.; Rani, M.; Arora, T. Recent advancements in organotin (IV) complexes as potent cytotoxic agents. Anti-Cancer. Agents Med. Chem., 2023, 23, 164-191.
  25. Awang, N.; Kamaludin, N.F. Cytotoxicity of diphenyltin(IV) diisopropyl dithiocarbamate compound on acute lymphoblastic leukemia cells, CCL-119 (CCRF-CEM). Preprints, 2022, 2022050149. doi: 10.20944/preprints202205.0149.v1
  26. Kamaludin, N.F.; Awang, N. Synthesis and characterisation of organotin (IV) N-ethyl-N-phenyldithiocarbamate compounds and the crystal structures of dibutyl-and triphenyltin (IV) N-ethyl-N-phenyldithiocarbamate. Res. J. Chem. Environ., 2014, 18, 99-107.
  27. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63. doi: 10.1016/0022-1759(83)90303-4 PMID: 6606682
  28. Singh, N.P.; McCoy, M.T.; Tice, R.R.; Schneider, E.L. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp. Cell Res., 1988, 175(1), 184-191. doi: 10.1016/0014-4827(88)90265-0 PMID: 3345800
  29. Antonenko, T.A.; Gracheva, Y.A.; Shpakovsky, D.B.; Vorobyev, M.A.; Mazur, D.M.; Tafeenko, V.A.; Oprunenko, Y.F.; Shevtsova, E.F.; Shevtsov, P.N.; Nazarov, A.A.; Milaeva, E.R. Biological activity of novel organotin compounds with a schiff base containing an antioxidant fragment. Int. J. Mol. Sci., 2023, 24(3), 2024. doi: 10.3390/ijms24032024 PMID: 36768345
  30. Mandal, A.; Ghosh, M.; Talukdar, D.; Dey, P.; Das, A.; Giri, S. Cytotoxicity and genotoxicity of tributyltin in the early embryonic chick, Gallus gallus domesticus. Mutat. Res. Genet. Toxicol. Environ. Mutagen., 2023, 889, 503656. doi: 10.1016/j.mrgentox.2023.503656 PMID: 37491115
  31. Syed Annuar, S.N.; Kamaludin, N.F.; Awang, N.; Chan, K.M. Triphenyltin(IV) dithiocarbamate compound induces genotoxicity and cytotoxicity in K562 human erythroleukemia cells primarily via mitochondria-mediated apoptosis. Food Chem. Toxicol., 2022, 168, 113336. doi: 10.1016/j.fct.2022.113336 PMID: 35963475
  32. Hunakova, L.; Macejova, D.; Toporova, L.; Brtko, J. Anticancer effects of tributyltin chloride and triphenyltin chloride in human breast cancer cell lines MCF-7 and MDA-MB-231. Tumour Biol., 2016, 37(5), 6701-6708. doi: 10.1007/s13277-015-4524-6 PMID: 26662104
  33. Sirajuddin, M.; Ali, S.; McKee, V.; Sohail, M.; Pasha, H. Potentially bioactive organotin(IV) compounds: Synthesis, characterization, in vitro bioactivities and interaction with SS-DNA. Eur. J. Med. Chem., 2014, 84, 343-363. doi: 10.1016/j.ejmech.2014.07.028 PMID: 25036793
  34. Adeyemi, J.; Onwudiwe, D. Antimicrobial and cytotoxicity studies of some organotin (IV) N-ethyl-N-phenyl dithiocarbamate complexes. Pol. J. Environ. Stud., 2020, 29(4), 2525-2532. doi: 10.15244/pjoes/111231
  35. Golonko, A.; Olichwier, A.J.; Swislocka, R.; Szczerbinski, L.; Lewandowski, W. Why do dietary flavonoids have a promising effect as enhancers of anthracyclines? hydroxyl substituents, bioavailability and biological activity. Int. J. Mol. Sci., 2022, 24(1), 391. doi: 10.3390/ijms24010391 PMID: 36613834
  36. Niu, L.; Li, Y.; Li, Q. Medicinal properties of organotin compounds and their limitations caused by toxicity. Inorg. Chim. Acta, 2014, 423, 2-13. doi: 10.1016/j.ica.2014.05.007
  37. Zhou, M.; Feng, M.; Fu, L.; Ji, L.; Zhao, J.; Xu, J. Toxicogenomic analysis identifies the apoptotic pathway as the main cause of hepatotoxicity induced by tributyltin. Food Chem. Toxicol., 2016, 97, 316-326. doi: 10.1016/j.fct.2016.09.027 PMID: 27678064
  38. Kumar, M.; Abbas, Z.; Siwach, P.; Sharma, J.; Rani, A.; Sharma, S.; Aggarwal, P.; Show, P-L.; Haque, S. Path of organotin complexes: Synthetic factors, mechanisms, and broad-spectrum biological influences. J. Adv. Biotechnol. Exp Ther., 2023, 6(2), 386-402.
  39. Damghani, T.; Moosavi, F.; Khoshneviszadeh, M.; Mortazavi, M.; Pirhadi, S.; Kayani, Z.; Saso, L.; Edraki, N.; Firuzi, O. Imidazopyridine hydrazone derivatives exert antiproliferative effect on lung and pancreatic cancer cells and potentially inhibit receptor tyrosine kinases including c-Met. Sci. Rep., 2021, 11(1), 3644. doi: 10.1038/s41598-021-83069-4 PMID: 33574356
  40. Ullah, H.; Previtali, V.; Mihigo, H.B.; Twamley, B.; Rauf, M.K.; Javed, F.; Waseem, A.; Baker, R.J.; Rozas, I. Structure-activity relationships of new Organotin(IV) anticancer agents and their cytotoxicity profile on HL-60, MCF-7 and HeLa human cancer cell lines. Eur. J. Med. Chem., 2019, 181, 111544. doi: 10.1016/j.ejmech.2019.07.047 PMID: 31374420
  41. Koch, A.; Tamez, P.; Pezzuto, J.; Soejarto, D. Evaluation of plants used for antimalarial treatment by the Maasai of Kenya. J. Ethnopharmacol., 2005, 101(1-3), 95-99. doi: 10.1016/j.jep.2005.03.011 PMID: 15878245
  42. Kim, K.; Yoo, H.J.; Jung, J.H.; Lee, R.; Hyun, J.K.; Park, J.H.; Na, D.; Yeon, J.H. Cytotoxic effects of plant sap-derived extracellular vesicles on various tumor cell types. J. Funct. Biomater., 2020, 11(2), 22. doi: 10.3390/jfb11020022 PMID: 32252412
  43. Hamid, A.; Aiyelaagbe, O.; Usman, L.; Ameen, O.; Lawal, A. Antioxidants: Its medicinal and pharmacological applications. Afr. J. Pure Appl. Chem., 2010, 4, 142-151.
  44. Seebacher, N.A.; Richardson, D.R.; Jansson, P.J. A mechanism for overcoming P-glycoprotein-mediated drug resistance: Novel combination therapy that releases stored doxorubicin from lysosomes via lysosomal permeabilization using Dp44mT or DpC. Cell Death Dis., 2016, 7(12), e2510-e2510. doi: 10.1038/cddis.2016.381 PMID: 27906178
  45. Kairuki, M.; Qiu, Q.; Pan, M.; Li, Q.; Zhou, J.; Ghaleb, H.; Huang, W.; Qian, H.; Jiang, C. Designed P-glycoprotein inhibitors with triazol-tetrahydroisoquinoline-core increase doxorubicin-induced mortality in multidrug resistant K562/A02 cells. Bioorg. Med. Chem., 2019, 27(15), 3347-3357. doi: 10.1016/j.bmc.2019.06.013 PMID: 31202598
  46. Farahana Kamaludin, N.; Aishah Zakaria, S.; Awang, N.; Mohamad, R.; Uttraphan Pim, N. Cytotoxicity assessment of organotin (IV)(2-metoxyethyl) methyldithiocarbamate compounds in human leukemia cell lines. Orient. J. Chem., 2017, 33(4), 1756-1766. doi: 10.13005/ojc/330420
  47. Ray, D.; Sarma, K.D.; Antony, A. Differential effects of tri-n-butylstannyl benzoates on induction of apoptosis in K562 and MCF-7 cells. IUBMB Life, 2000, 49(6), 519-525. doi: 10.1080/15216540050167061 PMID: 11032246
  48. Pantelić, NĐ; Zmejkovski, BB; Žižak, Ž; Banjac, NR; Božić, BĐ; Stanojković, TP; Kaluđerović, GN Design and in vitro biological evaluation of a novel organotin (IV) complex with 1-(4-carboxyphenyl)-3-ethyl-3-methylpyrrolidine-2, 5-dione. J. Chem. 2019, 2019.
  49. Syed Annuar, S.N.; Kamaludin, N.F.; Awang, N.; Chan, K.M.; Uttraphan Pim, N. Diorganotin(IV) N-methyl-N-phenethyldithio-carbamate compounds induce cytotoxicity via apoptosis in K562 human erythroleukaemia cells. Sains Malays., 2023, 52(5), 1513-1521. doi: 10.17576/jsm-2023-5205-14
  50. Sit, K.H.; Bay, B.H.; Wong, K.P. Reduced surface area in mitotic rounding of human chang liver cells. Anat. Rec., 1993, 235(2), 183-190. doi: 10.1002/ar.1092350202 PMID: 8420388
  51. Jiang, N.; Naz, S.; Ma, Y.; Ullah, Q.; Khan, M.Z.; Wang, J.; Lu, X.; Luosang, D.Z.; Tabassum, S.; Chatha, A.M.M.; Basang, W-D. An overview of comet assay application for detecting DNA damage in aquatic animals. Agriculture, 2023, 13(3), 623. doi: 10.3390/agriculture13030623
  52. Gajski, G. Ravlić, S.; Godschalk, R.; Collins, A.; Dusinska, M.; Brunborg, G. Application of the comet assay for the evaluation of DNA damage in mature sperm. Mutat. Res. Rev. Mutat. Res., 2021, 788, 108398. doi: 10.1016/j.mrrev.2021.108398 PMID: 34893163
  53. Møller, P.; Stopper, H.; Collins, A.R. Measurement of DNA damage with the comet assay in high-prevalence diseases: Current status and future directions. Mutagenesis, 2020, 35(1), 5-18. PMID: 31294794
  54. Rodríguez, R.; Gaivão, I.; Aguado, L.; Espina, M.; García, J.; Martínez-Camblor, P.; Sierra, L.M. The comet assay in drosophila: A tool to study interactions between DNA repair systems in DNA damage responses in vivo and ex vivo. Cells, 2023, 12(15), 1979. doi: 10.3390/cells12151979 PMID: 37566058
  55. Kuchařová, M.; Hronek, M.; Rybáková, K.; Zadák, Z.; Štětina, R.; Josková, V.; Patková, A. Comet assay and its use for evaluating oxidative DNA damage in some pathological states. Physiol. Res., 2019, 68(1), 1-15. doi: 10.33549/physiolres.933901 PMID: 30433808
  56. Alhmoud, J.F.; Woolley, J.F.; Al Moustafa, A.E.; Malki, M.I. DNA damage/repair management in cancers. Cancers, 2020, 12(4), 1050. doi: 10.3390/cancers12041050 PMID: 32340362
  57. Awang, N.; Kamaludin, N.F.; Hamid, A.; Mokhtar, N.W.N.; Rajab, N.F. Cytotoxicity of triphenyltin(IV) methyl- and ethylisopropyldithiocarbamate compounds in chronic myelogenus leukemia cell line (K-562). Pak. J. Biol. Sci., 2012, 15(17), 833-838. doi: 10.3923/pjbs.2012.833.838 PMID: 24163967
  58. Rostami, A.; Lambie, M.; Yu, C.W.; Stambolic, V.; Waldron, J.N.; Bratman, S.V. Senescence, necrosis, and apoptosis govern circulating cell-free DNA release kinetics. Cell Rep., 2020, 31(13), 107830. doi: 10.1016/j.celrep.2020.107830 PMID: 32610131
  59. Sun, Z.; Xue, L.; Li, Y.; Cui, G.; Sun, R.; Hu, M.; Zhong, G. Rotenone-induced necrosis in insect cells via the cytoplasmic membrane damage and mitochondrial dysfunction. Pestic. Biochem. Physiol., 2021, 173, 104801. doi: 10.1016/j.pestbp.2021.104801 PMID: 33771250
  60. Chigasova, A.K.; Ostrovskaya, L.A.; Korman, D.B. Induction of DNA structure damage in tumor cells by gold polyacrylate. Biophysics (Oxf.), 2023, 68(1), 6-12. doi: 10.1134/S0006350923010050
  61. Sharif, R.; Ghazali, A.R.; Rajab, N.F. DNA damaging effect of selected salted and fermented food products against chang liver cell. Jurnal Sains Kesihatan Malaysia, 2007, 5, 63-77.

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