Abstract
The anticancer activity of monensic acid (MonH) and its biometal(II) complexes [M(Mon)2(H2O)2](M = Mg, Ca, Mn, Co, Ni, Zn) was evaluated against cultured human permanent cell lines established from glioblastoma multiforme (8MGBA) and cancers of the lung (A549), breast (MCF-7), uterine cervix (HeLa) and liver (HepG2). The viability and proliferation of the non-tumor human embryonic cell line Lep3 was also tested. The investigations were carried out using a thiazolyl blue tetrazolium bromide test, neutral red uptake cytotoxicity assay, crystal violet staining, colony forming method and double staining with acridin orange and propidium iodide. The results obtained reveal that the compounds applied at concentrations of 0.5–25 µg mL−1 for 24–72 h decrease the viability and proliferation of the treated cells in a time- and concentration-dependent manner. The metal(II) complexes studied (especially those of Co(II), Ni(II) and Zn(II)) have been found to express stronger cytotoxic and cytostatic activities than the non-coordinated monensic acid. The non-tumor human cell line showed strong chemosensitivity towards compounds tested comparable to that of cultured human tumor cell lines. 
[1] A. Agtarap, J.W. Chamberlin, M. Pinkerton, L.K. Steinrauf, J. Am. Chem. Soc. 89, 5737 (1967) http://dx.doi.org/10.1021/ja00998a06210.1021/ja00998a062Search in Google Scholar
[2] B.C. Pressman, Ann. Rev. Biochem. 45, 501 (1976) http://dx.doi.org/10.1146/annurev.bi.45.070176.00244110.1146/annurev.bi.45.070176.002441Search in Google Scholar
[3] P.H. Stern, Clin. Orthop. Rel. Res. 122, 273 (1977) 10.1097/00003086-197701000-00041Search in Google Scholar
[4] P.C. Augustine, C.K. Smith, H.D. Danforth, M.D. Ruff, Poultry Sci. 66, 960 (1987) http://dx.doi.org/10.3382/ps.066096010.3382/ps.0660960Search in Google Scholar
[5] S.D. Folz, B.L. Lee, L.H. Nowakowski, G.A. Conder, Vet. Parasit. 28, 1 (1988) http://dx.doi.org/10.1016/0304-4017(88)90013-110.1016/0304-4017(88)90013-1Search in Google Scholar
[6] D.A. Kevin II, D.A.F. Meujo, M.T. Hamann, Exp. Opi. Drug Discov. 4, 109 (2009) http://dx.doi.org/10.1517/1746044080266144310.1517/17460440802661443Search in Google Scholar PubMed PubMed Central
[7] B.G. Cox, N. van Truong, J. Rzeszotarska, H. Schneider, J. Chem. Soc., Faraday Trans. I 80, 3275 (1984) http://dx.doi.org/10.1039/f1984800327510.1039/f19848003275Search in Google Scholar
[8] M. Mimouni, S. Perrier, I. Pointud, J. Juillard, J. Sol. Chem. 22, 769 (1993) http://dx.doi.org/10.1007/BF0064858110.1007/BF00648581Search in Google Scholar
[9] M. Mimouni, M. Hebrant, G. Dauphin, J. Juillard, J. Chem. Res. S6, 278 (1996) Search in Google Scholar
[10] F.G. Riddell, Chirality 14, 121 (2002) http://dx.doi.org/10.1002/chir.1005210.1002/chir.10052Search in Google Scholar PubMed
[11] W.H. Park et al., Intern. J. Cancer 101, 235 (2002) http://dx.doi.org/10.1002/ijc.1059210.1002/ijc.10592Search in Google Scholar PubMed
[12] W.H. Park et al., Brit. J. Haem. 119, 400 (2002) http://dx.doi.org/10.1046/j.1365-2141.2002.03834.x10.1046/j.1365-2141.2002.03834.xSearch in Google Scholar
[13] W.H. Park et al., Intern. J. Oncol. 22, 377 (2003) 10.1016/S0750-7658(03)00118-7Search in Google Scholar
[14] W.H. Park et al., Intern. J. Oncol. 22, 855 (2003) Search in Google Scholar
[15] W.H. Park, E.S. Kim, B.K. Kim, Y.Y. Lee, Intern. J. Oncology 23, 197 (2003) Search in Google Scholar
[16] J. Basque, M. Martel, R. Leduc, A.M. Cantin, Can. J. Physiol. Pharmacol. 86, 606 (2008) http://dx.doi.org/10.1139/Y08-06310.1139/Y08-063Search in Google Scholar
[17] G.C. Blobe, W.P. Schiemann, H.F. Lodish, N. Engl. J. Med. 342, 1350 (2000) http://dx.doi.org/10.1056/NEJM20000504342180710.1056/NEJM200005043421807Search in Google Scholar
[18] T. Griffin et al., J. Natl. Cancer Inst. 85, 292 (1993) http://dx.doi.org/10.1093/jnci/85.4.29210.1093/jnci/85.4.292Search in Google Scholar
[19] M.S. Shaik, T.L. Jackson, M. Singh, J. Pharm. Pharmacol. 55, 819 (2003) http://dx.doi.org/10.1211/00223570376595143810.1211/002235703765951438Search in Google Scholar
[20] M. Wu, Br. J. Cancer. 75, 1347 (1997) http://dx.doi.org/10.1038/bjc.1997.22810.1038/bjc.1997.228Search in Google Scholar
[21] M. Sehested, T. Skovsgaard, H. Roed, Biochem. Pharmacol. 37, 3305 (1988) http://dx.doi.org/10.1016/0006-2952(88)90643-010.1016/0006-2952(88)90643-0Search in Google Scholar
[22] W.D. Klohz, R.W. Steinkampf, Mol. Pharmacol. 34, 180 (1988) Search in Google Scholar
[23] N.K. Chirase, L.W. Greene, G.T. Schelling, F.M. Byers, J. Anim. Sci. 65, 1633 (1987) 10.2527/jas1987.6561633xSearch in Google Scholar PubMed
[24] K.A. Johnson, Diss. Abstr., Intern. B Sci. Eng. 48, 1855 (1988) Search in Google Scholar
[25] S.A. Hamidinia et al., J. Biol. Chem. 277, 38111 (2002) http://dx.doi.org/10.1074/jbc.M20559020010.1074/jbc.M205590200Search in Google Scholar PubMed
[26] I.N. Pantcheva et al., Curr. Drug Discov. Techn. 5, 154 (2008) http://dx.doi.org/10.2174/15701630878474624710.2174/157016308784746247Search in Google Scholar PubMed
[27] I.N. Pantcheva et al., BioMetals 23, 59 (2010) http://dx.doi.org/10.1007/s10534-009-9269-510.1007/s10534-009-9269-5Search in Google Scholar
[28] I.N. Pantcheva et al., Inorg. Chim. Acta 363, 1879 (2010) http://dx.doi.org/10.1016/j.ica.2010.02.00910.1016/j.ica.2010.02.009Search in Google Scholar
[29] J. Ivanova et al., Centr. Eur. J. Chem. 8, 852 (2010) http://dx.doi.org/10.2478/s11532-010-0067-210.2478/s11532-010-0067-2Search in Google Scholar
[30] R.I. Alexandrova, T. Zhivkova, I.N. Pantcheva, M.Io. Mitewa, Intern. J. Biol. Biomed. Eng. 5, 93 (2011) Search in Google Scholar
[31] M. R. Boyd, In: B. Teicher (Ed.), Anticancer Drug Development Cuide: Preclinical Screening, Clinical Trials and Approval (Humana Press Inc., Totowa, NJ, 1995) 23 Search in Google Scholar
[32] A. Perzelova et al., Neoplasma 42, 25 (1998) 10.1016/S0294-3506(99)80152-5Search in Google Scholar
[33] T. Mosmann, J. Immunol. Meth. 65, 55 (1983) http://dx.doi.org/10.1016/0022-1759(83)90303-410.1016/0022-1759(83)90303-4Search in Google Scholar
[34] E. Borenfreund, J. Puerner, Toxicol. Lett. 24, 119 (1985) http://dx.doi.org/10.1016/0378-4274(85)90046-310.1016/0378-4274(85)90046-3Search in Google Scholar
[35] K. Saotome, H. Morita, M. Umeda, Toxicol. In Vitro 3, 317 (1989) http://dx.doi.org/10.1016/0887-2333(89)90039-810.1016/0887-2333(89)90039-8Search in Google Scholar
[36] S.I.A. Wahab et al., J. Biomed. Biotechnol. 769568 (2009) Search in Google Scholar
[37] B.C. Pressman, M. Fashin, Ann. Rev. Pharm. Toxicol. 22, 465 (1982) http://dx.doi.org/10.1146/annurev.pa.22.040182.00234110.1146/annurev.pa.22.040182.002341Search in Google Scholar
[38] K. Nakazato, Y. Hatano, Biochim. Biophys. Acta 1064, 103 (1991) http://dx.doi.org/10.1016/0005-2736(91)90416-610.1016/0005-2736(91)90416-6Search in Google Scholar
[39] W.H. Zhu, T T. Loh, Biochim. Biophys. Acta — Mol. Cell Res. 1269, 122 (1995) http://dx.doi.org/10.1016/0167-4889(95)00102-X10.1016/0167-4889(95)00102-XSearch in Google Scholar
[40] S. Grinstein, D. Rotin, M.J. Mason, Biochim. Biophys. Acta 988, 73 (1989) http://dx.doi.org/10.1016/0304-4157(89)90004-X10.1016/0304-4157(89)90004-XSearch in Google Scholar
[41] M. Bental, C. Deutsch, Am. J. Physiol. 266, 541C (1994) 10.1152/ajpcell.1994.266.2.C541Search in Google Scholar
[42] G.N. Rao, N. de Roux, C. Sardet, J. Pouyssegur, B.C. Berk, J. Biol. Chem. 266, 13485 (1991) 10.1016/S0021-9258(18)92721-3Search in Google Scholar
[43] J.M. Cobo et al., J. Cell. Physiol. 175, 59 (1998) http://dx.doi.org/10.1002/(SICI)1097-4652(199804)175:1<59::AID-JCP7>3.0.CO;2-B10.1002/(SICI)1097-4652(199804)175:1<59::AID-JCP7>3.0.CO;2-BSearch in Google Scholar
[44] S.W. Jacob, In: S.W. Jakob, E.E. Rosenbaun, D.C. Wood (Eds.), Dimethyl sulfoxide, vol. 1. Basic concepts of DMSO (Marcel Dekker Ink., New York, 1971) 99 Search in Google Scholar
[45] N.C. Santos, J. Figueira-Coelho, J. Martins-Silva, C. Saldanha, Biochem. Pharm. 65, 1035 (2003) http://dx.doi.org/10.1016/S0006-2952(03)00002-910.1016/S0006-2952(03)00002-9Search in Google Scholar
[46] K.S. Smalley, M. Lioni, M. Herlyn, In Vitro Cell Dev. Biol. — Animal 42, 242 (2006) http://dx.doi.org/10.1290/0604027.110.1290/0604027.1Search in Google Scholar
[47] J. Lee et al., Small 5, 1213 (2009) Search in Google Scholar
[48] A.C. Souza et al., J. Vet. Med. A — Physiol. Pathol. Clin. Med. 52, 230 (2005) http://dx.doi.org/10.1111/j.1439-0442.2005.00728.x10.1111/j.1439-0442.2005.00728.xSearch in Google Scholar
[49] R. Alexandrova, Exp. Pathol. Parasitol. 4, 57 (2001) Search in Google Scholar
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