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BIAN N-Heterocyclic Gold Carbene Complexes induced cytotoxicity in human cancer cells via upregulating oxidative stress

  • Farooq, Muhammad (Bioproducts Research Chair, Department of Zoology, College of Science, King Saud University) ;
  • Taha, Nael Abu (Bioproducts Research Chair, Department of Zoology, College of Science, King Saud University) ;
  • Butorac, Rachel R (Department of Chemistry, The University of Texas at Austin) ;
  • Evans, Daniel A (Department of Chemistry, The University of Texas at Austin) ;
  • Elzatahry, Ahmed A (Materials Science and Technology Program, College of Arts and Sciences, Qatar University) ;
  • Wadaan, Mohammad AM (Bioproducts Research Chair, Department of Zoology, College of Science, King Saud University) ;
  • Cowley, Alan H (Department of Chemistry, The University of Texas at Austin)
  • Published : 2015.11.04

Abstract

Background: Nanoparticles of gold and silver are offering revolutionary changes in the field of cancer therapy. N-heterocyclic carbene (NHC) metal complexes possess diverse biological activities and are being investigated as potential chemotherapeutic agents. The purpose of this study was to examine the cytotoxicity and possible mechanisms of action of two types of newly synthesized nanofiber composites containing BIAN N-heterocyclic gold carbene complexes in two types of human cancer cells, namely breast cancer (MCF7) and liver cancer (HepG2) cells and also in normal human embryonic kidney cells (HEK 293). Materials and Methods: Cytotoxicity was assessed by MTT cell viability assay and oxidative stress by checking the total glutathione level. Results: Both compounds affected the cell survival of the tested cell lines at very low concentrations (IC50 values in the micro molar range) as compared to a well-known anti-cancer drug, 5 fluorouracil. A 60-80% depletion in total glutathione level was detected in treated cells. Conclusions: Reduction in total glutathione level is one of the biochemical pathways for the induction of oxidative stress which in turn could be a possible mechanism of action by which these compounds induce cytotoxicity in cancer cell lines. The in vitro toxicity towards cancer cells found here means that these molecules could be potential anticancer candidates.

Keywords

BIAN N-heterocyclic carbene complexes;nanofiber composite;cytotoxicity;oxidative stress

References

  1. Alfaro JM, Prades A, del Carmen Ramos M, et al (2010). Biomedical properties of a series of ruthenium-Nheterocyclic carbene complexes based on oxidant activity in vitro and assessment in vivo of biosafety in zebrafish embryos. Zebrafish, 7, 13-21. https://doi.org/10.1089/zeb.2009.0601
  2. Baker MV, Barnard PJ, Berners-Price SJ, et al (2006). Cationic, linear Au(i) N-heterocyclic carbene complexes: synthesis, structure and anti-mitochondrial activity. Dalton Transactions, 3708-15.
  3. Berners-Price SJ (2011). Activating platinum anticancer complexes with visible light. Angew Chem Int Ed Engl, 50, 804-5. https://doi.org/10.1002/anie.201004552
  4. Bourissou D, Guerret O, Gabbai FP, et al (2000). Stable Carbenes. Chemical Reviews, 100, 39-92. https://doi.org/10.1021/cr940472u
  5. Butorac RR, Al-Deyab SS, Cowley AH (2011). Antimicrobial properties of some bis(iminoacenaphthene (BIAN)- supported N-heterocyclic carbene complexes of silver and gold. Molecules, 16, 2285-92. https://doi.org/10.3390/molecules16032285
  6. Daduang J, Palasap A, Daduang S, et al (2015). Gallic acid enhancement of gold nanoparticle anticancer activity in cervical cancer cells. Asian Pac J Cancer Prev, 16, 169-74. https://doi.org/10.7314/APJCP.2015.16.1.169
  7. Droge T, Glorius F (2010). The measure of all rings-nheterocyclic carbenes. Angewandte Chemie-International Edition, 49, 6940-52. https://doi.org/10.1002/anie.201001865
  8. Elzatahry AA, Al-Enizi AM, Elsayed EA, et al (2012). Nanofiber composites containing N-heterocyclic carbene complexes with antimicrobial activity. Int J Nanomedicine, 7, 2829-32.
  9. Farooq M, El-Faham A, Khattab SN, et al (2014). Biological screening of novel derivatives of valproic acid for anticancer and antiangiogenic properties. Asian Pac J Cancer Prev, 15, 7785-92. https://doi.org/10.7314/APJCP.2014.15.18.7785
  10. Franco R, Cidlowski JA (2009). Apoptosis and glutathione: beyond an antioxidant. Cell Death Differ, 16, 1303-14. https://doi.org/10.1038/cdd.2009.107
  11. Gautier A, Cisnetti F (2012). Advances in metal-carbene complexes as potent anti-cancer agents. Metallomics, 4, 23-32. https://doi.org/10.1039/C1MT00123J
  12. Herrmann WA (2002). N-heterocyclic carbenes: a new concept in organometallic catalysis. Angew Chem Int Ed Engl, 41, 1290-309. https://doi.org/10.1002/1521-3773(20020415)41:8<1290::AID-ANIE1290>3.0.CO;2-Y
  13. Hickey JL, Ruhayel RA, Barnard PJ, et al (2008a). Mitochondriatargeted chemotherapeutics: the rational design of gold(I) N-heterocyclic carbene complexes that are selectively toxic to cancer cells and target protein selenols in preference to thiols. J Am Chem Soc, 130, 12570-1. https://doi.org/10.1021/ja804027j
  14. Hickey JL, Ruhayel RA, Barnard PJ, et al (2008b). Mitochondriatargeted chemotherapeutics: the rational design of gold(I) N-heterocyclic carbene complexes that are selectively toxic to cancer cells and target protein selenols in preference to thiols. J Am Chem Soc, 130, 12570-1. https://doi.org/10.1021/ja804027j
  15. Hindi KM, Panzner MJ, Tessier CA, et al (2009). The medicinal applications of imidazolium carbene-metal complexes. Chemical Reviews, 109, 3859-84. https://doi.org/10.1021/cr800500u
  16. Islamian JP, Hatamian M, Rashidi MR (2015). Nanoparticles promise new methods to boost oncology outcomes in breast cancer. Asian Pac J Cancer Prev, 16, 1683-6. https://doi.org/10.7314/APJCP.2015.16.5.1683
  17. Liu W, Gust R (2013a). Metal N-heterocyclic carbene complexes as potential antitumor metallodrugs. Chem Soc Rev, 42, 755-73. https://doi.org/10.1039/C2CS35314H
  18. Liu WK, Gust R (2013b). Metal N-heterocyclic carbene complexes as potential antitumor metallodrugs. Chem Soc Rev, 42, 755-73. https://doi.org/10.1039/C2CS35314H
  19. Manke A, Wang LY, Rojanasakul Y (2013). Mechanisms of nanoparticle-induced oxidative stress and toxicity. biomed research international.
  20. Mateo D, Morales P, Avalos A, et al (2014). Oxidative stress contributes to gold nanoparticle-induced cytotoxicity in human tumor cells. Toxicology Mechanisms and Methods, 24, 161-72. https://doi.org/10.3109/15376516.2013.869783
  21. Melaiye A, Simons RS, Milsted A, et al (2004). Formation of water-soluble pincer silver(I)-carbene complexes: a novel antimicrobial agent. J Med Chem, 47, 973-7. https://doi.org/10.1021/jm030262m
  22. Nardon C, Boscutti G, Fregona D (2014). Beyond platinums: gold complexes as anticancer agents. Anticancer Res, 34, 487-92.
  23. Oehninger L, Stefanopoulou M, Alborzinia H, et al (2013). Evaluation of arene ruthenium(II) N-heterocyclic carbene complexes as organometallics interacting with thiol and selenol containing biomolecules. Dalton Trans, 42, 1657-66. https://doi.org/10.1039/C2DT32319B
  24. Ozdemir I, Temelli N, Gunal S, et al (2010). Gold(I) complexes of N-heterocyclic carbene ligands containing benzimidazole: synthesis and antimicrobial activity. Molecules, 15, 2203-10. https://doi.org/10.3390/molecules15042203
  25. Pervaiz S, Clement MV (2002). A permissive apoptotic environment: function of a decrease in intracellular superoxide anion and cytosolic acidification. Biochem Biophys Res Commun, 290, 1145-50. https://doi.org/10.1006/bbrc.2001.6274
  26. Rubbiani R, Can S, Kitanovic I, et al (2011). Comparative in vitro evaluation of n-heterocyclic carbene Gold(I) complexes of the benzimidazolylidene type. J Med Chem, 54, 8646-57. https://doi.org/10.1021/jm201220n
  27. Selim ME, Hendi AA (2012). Gold nanoparticles induce apoptosis in MCF-7 human breast cancer cells. Asian Pac J Cancer Prev, 13, 1617-20. https://doi.org/10.7314/APJCP.2012.13.4.1617
  28. Tedesco S, Doyle H, Blasco J, et al (2010). Oxidative stress and toxicity of gold nanoparticles in Mytilus edulis. Aquatic Toxicology, 100, 178-86. https://doi.org/10.1016/j.aquatox.2010.03.001
  29. Teyssot ML, Jarrousse AS, Manin M, et al (2009). Metal-NHC complexes: a survey of anti-cancer properties. Dalton Transactions, 6894-902.
  30. Vasudevan KV, Butorac RR, Abernethy CD, et al (2010). Synthesis and coordination compounds of a bis(imino) acenaphthene (BIAN)-supported N-heterocyclic carbene. Dalton Transactions, 39, 7401-8. https://doi.org/10.1039/c0dt00278j
  31. Weskamp T, Kohl FJ, Hieringer W, et al (1999). Highly active ruthenium catalysts for olefin metathesis: the synergy of n-heterocyclic carbenes and coordinatively labile ligands. Angew Chem Int Ed Engl, 38, 2416-9. https://doi.org/10.1002/(SICI)1521-3773(19990816)38:16<2416::AID-ANIE2416>3.0.CO;2-#

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