ZN(II)/AU(I) AND ZN(II)/AG(I) COMPLEXES WITH SALEN SCHIFF BASE EXPRESS PROMISING CYTOTOXIC ACTIVITY IN HUMAN CANCER CELLS

  • Tanya Zhivkova Department of , Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria.
  • Gabriela Marinescu Department of, Institute of Physical Chemistry “Ilie Murgulescu,” Romanian Academy, Bucharest, Romania.
  • Lora Dyakova Department of , Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
  • Daniela Cristina Culita Department of, Institute of Physical Chemistry “Ilie Murgulescu,” Romanian Academy, Bucharest, Romania.
  • Rossen Spasov Department of , Faculty of Medicine, Sofia University “St. Kliment Ohridski,” Sofia, Bulgaria.
  • Pavel Mitrenga BB - NCIPD Ltd., Sofia, Bulgaria.
  • Reni Kalfin Department of , Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
  • Luminita Patron Department of, Institute of Physical Chemistry “Ilie Murgulescu,” Romanian Academy, Bucharest, Romania.
  • Radostina Alexandrova Department of , Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria.

Abstract

Objective: The aim of our study was to evaluate the influence of two complexes of Zn(II)/Au(I) and Zn(II)/Ag(I) with Schiff base ligand (H2Salen) obtained from the condensation reaction between salicylaldehyde and ethylenediamine (abbreviated ZnSalenAu, ZnSalenAg) on viability and proliferation of cultured human cancer cells.

Methods: The following cell lines were used as model systems: Human cervical carcinoma (cervical carcinoma), A549 (non-small cell lung cancer [NSCLC]), glioblastoma multiforme (8MGBA), and A431 (squamous cell carcinoma) and its multidrug-resistant (MDR) clones A431-MDR, A431-MRP, and A431-ABCG2 that express mdr1, mrp1, or abcg2 gene, respectively. The investigations were performed by thiazolyl blue tetrazolium bromide test, neutral red uptake cytotoxicity assay, crystal violet staining, hematoxylin and eosin staining, double staining with acridine orange, and propidium iodide in short-term experiments (12–72 h, with monolayer cell cultures) as well as colony-forming method in long-term experiments (25 days, with three dimensional cancer cell colonies).

Results: The results obtained revealed that ZnSalenAu and ZnSalenAg decreased significantly viability and proliferation of the treated cells in a time- and concentration-dependent manner being more active as compared to the free ligand H2Salen.

Conclusion: The present study demonstrates for the 1st time the ability of two heterometallic complexes ZnSalenAu and ZnSalenAg to decrease significantly viability and proliferation of cultured cell lines established from some of the most common and aggressive human cancers (NSCLC, carcinoma of uterine cancer, 8MGBA, and squamous cell carcinoma) as well as MDR cancer cells.

Keywords: Cytotoxic activity, Human cancer cell lines, H2Salen, Schiff bases, Zn(II)/Au(I), Zn(II)/Ag(I) complexes.

References

1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer 2012;49:1374-403.
2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A, et al. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108.
3. Ali R, Mirza Z, Ashraf GM, Kamal MA, Ansari SA, Damanhouri GA, et al. New anticancer agents: Recent developments in tumor therapy. Anticancer Res 2012;32:2999-3005.
4. Gupta M, Dahiya J, Marwaha R, Dureja H. Therapies in cancer treatment: An overview. Int J Pharm Pharm Sci 2015;7:1-9.
5. Desoize B. Metals and metal compounds in cancer treatment. Anticancer Res 2004;24:1529-44.
6. Ndagi U, Mhlongo N, Soliman ME. Metal complexes in cancer therapy-an update from drug design perspective. Drug Des Devel Ther 2017;11:599-616.
7. Banti CN, Hadjikakou SK. Anti-proliferative and anti-tumor activity of silver(I) compounds. Metallomics 2013;5:569-96.
8. Liu JJ, Galettis P, Farr A, Maharaj L, Samarasinha H, McGechan AC, et al. In vitro antitumour and hepatotoxicity profiles of au(I) and ag(I) bidentate pyridyl phosphine complexes and relationships to cellular uptake. J Inorg Biochem 2008;102:303-10.
9. Thati B, Noble A, Creaven BS, Walsh M, McCann M, Kavanagh K, et al. A study of the role of apoptotic cell death and cell cycle events mediating the mechanism of action of 6-hydroxycoumarin- 3-carboxylatosilver in human malignant hepatic cells. Cancer Lett 2007;250:128-39.
10. Thati B, Noble A, Creaven BS, Walsh M, McCann M, Kavanagh K, et al. In vitro anti-tumour and cyto-selective effects of coumarin-3- carboxylic acid and three of its hydroxylated derivatives, along with their silver-based complexes, using human epithelial carcinoma cell lines. Cancer Lett 2007;248:321-31.
11. Zhu HL, Zhang XM, Liu XY. Clear Ag-Ag bonds in three sil-ver(I) carboxylate complexes with high cytotoxicity properties. Inorg Chem Commun 2003;6:1113-6.
12. Messori L, Marcon G. Gold complexes in the treatment of rheumatoid arthritis. Met Ions Biol Syst 2004;41:279-304.
13. Kostova I. Gold coordination complexes as anticancer agents. Anticancer Agents Med Chem 2006;6:19-32.
14. Messori L, Marcon G. Gold complexes as antitumor agents. Met Ions Biol Syst 2004;42:385-424.
15. Khalid N, Ahmed A, Bhatti MS, Randhawa MA, Ahmad A, Rafaqat R, et al. A question mark on zinc deficiency in 185 million people in Pakistan-possible way out. Crit Rev Food Sci Nutr 2014;54:1222-40.
16. Maret W. Zinc and human disease. Met Ions Life Sci 2013;13:389-414.
17. Prasad AS. Discovery of human zinc deficiency: Its impact on human health and disease. Adv Nutr 2013;4:176-90.
18. Prasad AS. Zinc: Role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab Care 2009;12:646-52.
19. Costello LC, Franklin RB. Zinc is decreased in prostate cancer: An established relationship of prostate cancer! J Biol Inorg Chem 2011;16:3-8.
20. Prasad AS, Beck FW, Snell DC, Kucuk O. Zinc in cancer prevention. Nutr Cancer 2009;61:879-87.
21. Adhikari A, Kumari N, Adhikari M, Kumar N, Tiwari AK, Shukla A, et al. Zinc complex of tryptophan appended 1,4,7,10-tetraazacyclododecane as potential anticancer agent: Synthesis and evaluation. Bioorg Med Chem 2017;25:3483-90.
22. Alexandrova R, Rashkova G, Salkova D, Sainova I. Something more about zinc. Exp Pathol Parasitol 2002;5:17-24.
23. Milosavljevic V, Haddad Y, Merlos Rodrigo MA, Moulick A, Polanska H, Hynek D, et al. The zinc-schiff base-novicidin complex as a potential prostate cancer therapy. PLoS One 2016;11:e0163983.
24. Drake PL, Hazelwood KJ. Exposure-related health effects of silver and silver compounds: A review. Ann Occup Hyg 2005;49:575-85.
25. Jones G, Brooks PM. Injectable gold compounds: An overview. Br J Rheumatol 1997;24:633-8.
26. Al Zoubi W. Biological activities of Schiff bases and their complexes: A review of recent works. Int J Org Chem 2013;3:73-95.
27. Arulmurugan S, Kavitha PH, Venkatraman BR. Biological activities of Schiff base and its complexes: A review. Rasayan J Chem 2010;3:385-410.
28. Gaikwad VK, Yadav UM. Metal complexes of Schiff bases. Sch Res J Interdiscip Stud 2016;3:2225-34.
29. Qin W, Long S, Panunzio M, Biondi S. Schiff bases: A short survey on an evergreen chemistry tool. Molecules 2013;18:12264-89.
30. Maanvizhi S, Boppana T, Krishnan C, Arumugam G. Metal complexes in the management of diabetes mellitus: A new therapeutic strategy. Int J Pharm Pharm Sci 2014;6:40-4.
31. Marinescu G, Madalan AM, Andruh M. New heterometallic coordination polymers based on zinc(II) complexes with Schiff-base ligands and dicyanometallates: Synthesis, crystal structures, and luminescent properties. J Coord Chem 2015;68:479.
32. Alexandrov I, Toshkova R, Alexandrov M, Dimitrov T, Sotirov N. Two tumor-associated membrane antigens defined by monoclonal antibodies in a transplantable sarcoma induced by Rous sarcoma virus in rat. Neoplasma 1996;43:275-82.
33. Alexandrov I, Toshkova R, Alexandrov M, Dimitrov T, Sotirov N. Tumor-associated antigens on rat sarcoma cells identified by monoclonal antibodies. Exp Oncol 1996;18:43-50.
34. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55-63.
35. Borenfreund E, Puerner JA. Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol Lett 1985;24:119-24.
36. Saotome K, Morita H, Umeda M. Cytotoxicity test with simplified crystal violet staining method using microtitre plates and its application to injection drugs. Toxicol In Vitro 1989;3:317-21.
37. Abdel Wahab SI, Abdul AB, Alzubairi AS, Mohamed Elhassan M, Mohan S. In vitro ultramorphological assessment of apoptosis induced by zerumbone on (HeLa). J Biomed Biotechnol 2009;2009:769568.
38. Liu CS, Chen PQ, Chang Z, Wang JJ, Yan LF, Sun HW, et al. A photoluminescent hexanuclear silver(I) complex exhibiting C–H Ag close interactions. Inorg Chem Commun 2008;11:159-63.
39. Levinger I, Ventura Y, Vago R. Life is three dimensional-as in vitro cancer cultures should be. Adv Cancer Res 2014;121:383-414.
40. Ravi M, Paramesh V, Kaviya SR, Anuradha E, Solomon FD. 3D cell culture systems: Advantages and applications. J Cell Physiol 2015;230:16-26.
41. Liu J, Ma S. Recent development in the discovery of anaplastic lymphoma kinase (ALK) inhibitors for non-small cell lung cancer. Curr Med Chem 2017;24:590-613.
42. Banelli B, Forlani A, Allemanni G, Morabito A, Pistillo MP, Romani M, et al. MicroRNA in glioblastoma: An overview. Int J Genomics 2017;2017:7639084.
43. Candolfi M, Curtin JF, Nichols WS, Muhammad AG, King GD, Pluhar GE, et al. Intracranial glioblastoma models in preclinical neuro-oncology: Neuropathological characterization and tumor progression. J Neurooncol 2007;85:133-48.
44. Begicevic RR, Falasca M. ABC transporters in cancer stem cells: Beyond chemoresistance. Int J Mol Sci 2017;18:2362.
45. Kartal-Yandim M, Adan-Gokbulut A, Baran Y. Molecular mechanisms of drug resistance and its reversal in cancer. Crit Rev Biotechnol 2016;36:716-26.
46. Bonanni P, Levi M, Latham NB, Bechini A, Tiscione E, Lai P, et al. An overview on the implementation of HPV vaccination in Europe. Hum Vaccin 2011;7 Suppl:128-35.
47. Tierney B, Westin SN, Schlumbrecht MP, Ramirez PT. Early cervical neoplasia: Advances in screening and treatment modalities. Clin Adv Hematol Oncol 2010;8:547-55.
48. Masters JR. HeLa cells 50 years on: The good, the bad and the ugly. Nat Rev Cancer 2002;2:315-9.
49. Vertrees RA, Goodwin TJ, Jordan JM. Tissue culture models. In: Zanger DS, Popper HH, Jagirdar J, Haque AK, Cagle PT, Barrios R, editors. Molecular Pathology of Lung Diseases. New York: Springer Science and Business Media, LLC; 2008. p. 150-68.
Statistics
68 Views | 103 Downloads
How to Cite
Zhivkova, T., G. Marinescu, L. Dyakova, D. Cristina Culita, R. Spasov, P. Mitrenga, R. Kalfin, L. Patron, and R. Alexandrova. “ZN(II)/AU(I) AND ZN(II)/AG(I) COMPLEXES WITH SALEN SCHIFF BASE EXPRESS PROMISING CYTOTOXIC ACTIVITY IN HUMAN CANCER CELLS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 1, Jan. 2019, pp. 458-64, doi:10.22159/ajpcr.2019.v12i1.28403.
Section
Original Article(s)