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Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

The In Vitro and In Vivo Antitumour Activities of Nitrosyl Ruthenium Amine Complexes

Renata Z. Osti A D , Fabiana A. Serrano C D , Thaysa Paschoalin B , Mariana H. S. Massaoka B , Luiz R. Travassos B , Daniela R. Truzzi A , Elaine G. Rodrigues C E and Douglas W. Franco A E F
+ Author Affiliations
- Author Affiliations

A Departamento de Química e Física Molecular, Instituto de Química de São Carlos – Universidade de São Paulo (USP), São Carlos, SP 13560-970, Brazil.

B Unidade de Oncologia Experimental, Disciplina de Biologia Celular, Departamento de Microbiologia, Imunologia e Parasitologia – Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, SP 04023-062, Brazil.

C Laboratório de Imunobiologia do Cancer, Disciplina de Biologia Celular, Departamento de Microbiologia, Imunologia e Parasitologia – Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, SP 04023-062, Brazil.

D These two authors contributed equally to this work.

E These two authors contributed equally to this work.

F Corresponding author. Email: douglas@iqsc.usp.br

Australian Journal of Chemistry 65(9) 1333-1341 https://doi.org/10.1071/CH12245
Submitted: 17 May 2012  Accepted: 8 July 2012   Published: 4 September 2012

Abstract

Ruthenium compounds of the type trans-[Ru(NO)(NH3)4(L)]X3, L = N-heterocyclic ligands, P(OEt)3, SO32–, X = BF4 or PF6, or [Ru(NO)Hedta], were tested for antitumour activity in vitro against murine melanoma and human tumour cells. The ruthenium complexes induced DNA fragmentation and morphological alterations suggestive of necrotic tumour cell death. The calculated IC50 values were lower than 100 μM. Complexes for which L = isn or imN were partially effective in vivo in a syngeneic model of murine melanoma B16F10, increasing animal survival. In addition, the same ruthenium complexes effectively inhibited angiogenesis of HUVEC cells in vitro. The results suggest that these nitrosyl complexes are a promising platform to be explored for the development of novel antitumour agents.


References

[1]  E. S. Antonarakis, A. Emadi, Cancer Chemother. Pharmacol. 2010, 66, 1.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXkslalt7Y%3D&md5=c8f3f52579ebb0776754d0683ec123ddCAS |

[2]  A. Bergamo, G. Sava, Dalton Trans. 2007, 1267.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjtFyhs7s%3D&md5=0f7dc9c2b0b79ab704c2d190882b6d1bCAS |

[3]  P. C. Ford, J. Bourassa, K. Miranda, B. Lee, I. Lorkovic, S. Boggs, S. Kudo, L. Laverman, Coord. Chem. Rev. 1998, 171, 185.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXjsFOitbc%3D&md5=e4e9977c4447b6ccade88c1004634bedCAS |

[4]  G. M. Halpenny, K. R. Gandhi, P. K. Mascharak, ACS Med. Chem. Lett. 2010, 1, 180.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXlsVSksLY%3D&md5=947aa4ac9b5102fd2ae6b261e8e13744CAS |

[5]  A. Levina, A. Mitra, P. A. Lay, Metallomics 2009, 1, 458.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXlslWlurg%3D&md5=a711b147f1604a5c41a49579d3cd2ca1CAS |

[6]  M. M. Liu, Z. J. Lim, Y. Y. Gwee, A. Levina, P. A. Lay, Angew. Chem. Int. Ed. 2010, 49, 1661.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXisVakt7o%3D&md5=822e4e4722d10bb0e48e9c2b143a986dCAS |

[7]  M. J. Rose, P. K. Mascharak, Curr. Opin. Chem. Biol. 2008, 12, 238.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXlslKltr4%3D&md5=2d216726ef59b603a071328c9b6a042fCAS |

[8]  Y. C. Boo, H. J. Kim, H. Song, D. Fulton, W. Sessa, H. Jo, Free Radic. Biol. Med. 2006, 41, 144.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xls1ars7g%3D&md5=87775aeabbe49a2586521983fc680fbfCAS |

[9]  D. R. Hyduke, J. C. Liao, Am. J. Physiol. Heart Circ. Physiol. 2005, 288, H2390.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXktlShtbc%3D&md5=44e7be388b3f201a24cec122c1d1458bCAS |

[10]  M. J. Rose, P. K. Mascharak, Coord. Chem. Rev. 2008, 252, 2093.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtVagtbjI&md5=67bd75f70cd9ca003cc7ec2f11935ad0CAS |

[11]  T. Yamamoto, R. J. Bing, Proc. Soc. Exp. Biol. Med. 2000, 225, 200.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXosVWhs7Y%3D&md5=4e5504f7caa26964dbb3d879c8eaa613CAS |

[12]  H. Yasuda, Nitric Oxide-Biol. Ch. 2008, 19, 205.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXoslWntL8%3D&md5=069042ba88e35ef2bcfba48352bf541bCAS |

[13]  R. G. Knowles, S. Moncada, Biochem. J. 1994, 298, 249.
         | 1:CAS:528:DyaK2cXitlyksbg%3D&md5=50982b326f0dbeeab510255741e638b2CAS |

[14]  P. Pagliaro, Life Sci. 2003, 73, 2137.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXmsVeju7s%3D&md5=bebf3a6379a9cd43ca3c74d91a310409CAS |

[15]  S. L. Elfering, T. M. Sarkela, C. Giulivi, J. Biol. Chem. 2002, 277, 38079.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xns1Cgurg%3D&md5=c75816cfe086ce8ffc2b1257782b588fCAS |

[16]  P. S. Brookes, Mitochondrion 2004, 3, 187.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhvVOrtrs%3D&md5=eb4b159d8cbfbc3b8301f97eb3a5be75CAS |

[17]  L. J. Ignarro, J. Mol. Cell. Cardiol. 2007, 43, 409.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtFWit7fP&md5=a9b02e7753efab3c447daa8e73ca61cfCAS |

[18]  Z. Lacza, E. Pankotai, A. Csordas, D. Geroo, L. Kiss, E. M. Horvath, M. Kollai, D. W. Busija, C. Szabo, Nitric Oxide-Biol. Ch. 2006, 14, 162.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtFWgtL8%3D&md5=c560db1f065f495fbf49b8b7cf0a0dcfCAS |

[19]  B. Bonavida, S. Khineche, S. Huerta-Yepez, H. Garban, Drug Resist. Update 2006, 9, 157.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XoslOguro%3D&md5=81f98f36b937b8a5bed09d8b765a59f7CAS |

[20]  J. A. Coulter, H. O. McCarthy, J. Xiang, W. Roedl, E. Wagner, T. Robson, D. G. Hirst, Nitric Oxide-Biol. Ch. 2008, 19, 192.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXoslWnt7c%3D&md5=eebaa1075e6394bab80a6a195069bba0CAS |

[21]  H. Erbas, N. Aydogdu, U. Usta, O. Erten, Cell Biol. Int. 2007, 31, 1414.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVWmsLzO&md5=9874701732fa165871b35930879ca88dCAS |

[22]  D. Fukumura, S. Kashiwagi, R. K. Jain, Nat. Rev. Cancer 2006, 6, 521.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XmtFehu7Y%3D&md5=12233effecf981c6eab04210a4b215acCAS |

[23]  S. Mocellin, V. Bronte, D. Nitti, Med. Res. Rev. 2007, 27, 317.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXmtVGrt7g%3D&md5=38f2e7aa1d5ebd389e7b6ba08a532d51CAS |

[24]  C. Perrotta, S. Falcone, A. Capobianco, A. Camporeale, C. Sciorati, C. De Palma, A. Pisconti, P. Rovere-Querini, M. Bellone, A. A. Manfredi, E. Clementi, Cancer Res. 2004, 64, 3767.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXksVKgurY%3D&md5=9ff325a637badbac65ec9f1fc34dbecdCAS |

[25]  D. Liao, R. S. Johnson, Cancer Metastasis Rev. 2007, 26, 281.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXotFWrtLw%3D&md5=a7d69a91fae6a05babcd62162e94088dCAS |

[26]  J. O. Lundberg, E. Weitzberg, M. T. Gladwin, Nat. Rev. Drug Discovery 2008, 7, 156.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhs1Khsrw%3D&md5=08e8d55e6aba13eed2e64592cc364929CAS |

[27]  G. F. P. de Souza, J. K. U. Yokoyama-Yasunaka, A. B. Seabra, D. C. Miguel, M. G. de Oliveira, S. R. B. Uliana, Nitric Oxide-Biol. Ch. 2006, 15, 209.
         | Crossref | GoogleScholarGoogle Scholar |

[28]  A. Weyerbrock, B. Baumer, A. Papazoglou, J. Neurosurg. 2009, 110, 128.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsV2lsro%3D&md5=bfd0992f97f48087757b01241df67fb3CAS |

[29]  E. Tfouni, F. G. Doro, L. E. Figueiredo, J. C. M. Pereira, G. Metzker, D. W. Franco, Curr. Med. Chem. 2010, 17, 3643.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsVGqu7jL&md5=84ce0b189859f0e9f0b48d117c1eb9a6CAS |

[30]  L. G. F. Lopes, E. E. Castellano, A. G. Ferreira, C. U. Davanzo, M. J. Clarke, D. W. Franco, Inorg. Chim. Acta 2005, 358, 2883.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXltVars74%3D&md5=11d2ae73095b6fb3c5f91016d93c602fCAS |

[31]  E. Tfouni, M. Krieger, B. R. McGarvey, D. W. Franco, Coord. Chem. Rev. 2003, 236, 57.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXkvVyruw%3D%3D&md5=e501da9776f16e0fa6dafb6ccb3be079CAS |

[32]  J. C. Toledo, H. A. S. Silva, M. Scarpellini, V. Mori, A. J. Camargo, M. Bertotti, D. W. Franco, Eur. J. Inorg. Chem. 2004, 1879.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXktVGgtL4%3D&md5=db8229300409456e32a42e8fbbbb8a11CAS |

[33]  D. R. Truzzi, A. G. Ferreira, S. C. da Silva, E. E. Castellano, F. D. Chagas Alves Lima, D. W. Franco, Dalton Trans. 2011, 40, 12917.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsFCmt73I&md5=622b903a0fd7cc0c9e31ce8c09f0f269CAS |

[34]  R. Scatena, P. Bottoni, A. Pontoglio, B. Giardina, Curr. Med. Chem. 2010, 17, 61.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsVSmt7s%3D&md5=580f9ec3fa08677cdf854c383730c55aCAS |

[35]  S. J. Lunt, N. Chaudary, R. P. Hill, Clin. Exp. Metastasis 2009, 26, 19.
         | Crossref | GoogleScholarGoogle Scholar |

[36]  J. C. M. Pereira, V. Carregaro, D. L. Costa, J. S. da Silva, F. Q. Cunha, D. W. Franco, Eur. J. Med. Chem. 2010, 45, 4180.
         | Crossref | GoogleScholarGoogle Scholar |

[37]  J. J. Silva, A. L. Osakabe, W. R. Pavanelli, J. S. Silva, D. W. Franco, Br. J. Pharmacol. 2007, 152, 112.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXpsFOjurc%3D&md5=216db3b01e9f1891da12065d16620219CAS |

[38]  J. J. Silva, W. R. Pavanelli, J. C. Pereira, J. S. Silva, D. W. Franco, Antimicrob. Agents Chemother. 2009, 53, 4414.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXht1KkurjM&md5=6d06a4a90a37df25844831013b26a085CAS |

[39]  P. G. Zanichelli, H. F. G. Estrela, R. C. Spadari-Bratfisch, D. M. Grassi-Kassisse, D. W. Franco, Nitric Oxide-Biol. Ch. 2007, 16, 189.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVaqtLs%3D&md5=72294474399f219720382006aba7e183CAS |

[40]  E. Tfouni, D. R. Truzzi, A. Tavares, A. J. Gomes, L. E. Figueiredo, D. W. Franco, Nitric Oxide-Biol. Ch. 2012, 26, 38.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtFOisrg%3D&md5=77a6943a4d18b798454bcb08f4d6bef2CAS |

[41]  J. A. Rodriguez, A. Souza-Torsoni, D. W. Franco, M. Haun, in XXVI Reunião Anual da Sociedade Brasileira de Bioquímica e Biologia Molecular 1997, Caxambú, Minas Gerais.

[42]  S. Ambs, W. G. Merriam, W. P. Bennett, E. Felley-Bosco, M. O. Ogunfusika, S. M. Oser, S. Klein, P. G. Shields, T. R. Billiar, C. C. Harris, Cancer Res. 1998, 58, 334.
         | 1:CAS:528:DyaK1cXnt1ajtA%3D%3D&md5=e7c72dde478fdebcb67da724b5c3ce4bCAS |

[43]  A. Bergamo, C. Gaiddon, J. H. M. Schellens, J. H. Beijnen, G. Sava, J. Inorg. Biochem. 2012, 106, 90.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsFOgtbfN&md5=ca3c50f2daf2447248817302bf99d5ffCAS |

[44]  A. Bergamo, G. Sava, Dalton Trans. 2011, 40, 7817.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXptleqs7c%3D&md5=5c4d8821a89c2a7e6f9add22486dd3feCAS |

[45]  S. Huerta, S. Chilka, B. Bonavida, Int. J. Oncol. 2008, 33, 909.
         | 1:CAS:528:DC%2BD1cXhsVaiu77F&md5=da2e697e8723b40e952dec06d4ed5cb8CAS |

[46]  H. M. Qiu, F. W. Orr, D. Jensen, H. H. Wang, A. R. McIntosh, B. B. Hasinoff, D. M. Nance, S. Pylypas, K. Qi, C. Song, R. J. Muschel, A. B. Al-Mehdi, Am. J. Pathol. 2003, 162, 403.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXhtlKrurw%3D&md5=1dbe3cb5c1238dfd855f07670634e815CAS |

[47]  H. M. Wang, A. R. McIntosh, B. B. Hasinoff, E. S. Rector, N. Ahmed, D. M. Nance, F. W. Orr, Cancer Res. 2000, 60, 5862.
         | 1:CAS:528:DC%2BD3cXnvVSnt7c%3D&md5=73f7864e0185a61c81b39e1ea38676d2CAS |

[48]  B. Bonavida, S. Baritaki, S. Huerta-Yepez, M. I. Vega, D. Chatterjee, K. Yeung, Nitric Oxide-Biol. Ch. 2008, 19, 152.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXoslWnt70%3D&md5=65edbf49fed7a8da973b0f5ccaab3efeCAS |

[49]  A. Jarry, L. Charrier, C. Bou-Hanna, M. C. Devilder, W. Crussaire, M. G. Denis, G. Vallette, C. L. Laboisse, Cancer Res. 2004, 64, 4227.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXkvFWlsLs%3D&md5=42803061dc40192f5e74186289e208fdCAS |

[50]  C. N. Lunardi, R. S. da Silva, L. M. Bendhack, Braz. J. Med. Biol. Res. 2009, 42, 87.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjvV2jsbw%3D&md5=5035b49d69ddd8247fa6db030478c69bCAS |

[51]  J. S. Royle, J. A. Ross, I. Ansell, P. Bollina, D. N. Tulloch, F. K. Habib, J. Urol. 2004, 172, 338.
         | Crossref | GoogleScholarGoogle Scholar |

[52]  F. A. Serrano, A. L. Matsuo, P. T. Monteforte, A. Bechara, S. S. Smaili, D. P. Santana, T. Rodrigues, F. V. Pereira, L. S. Silva, J. Machado, E. L. Santos, J. B. Pesquero, R. M. Martins, L. R. Travassos, A. C. Caires, E. G. Rodrigues, BMC Cancer 2011, 11, 296.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtVShtLfE&md5=867857599d4d025ea2e3a2569504e4d1CAS |

[53]  P. G. Zanichelli, A. M. Miotto, H. F. G. Estrela, F. R. Soares, D. M. Grassi-Kassisse, R. C. Spadari-Bratfisch, E. E. Castellano, F. Roncaroli, A. R. Parise, J. A. Olabe, A. R. M. S. de Brito, D. W. Franco, J. Inorg. Biochem. 2004, 98, 1921.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXptlOktLg%3D&md5=a61bf3542295f85b42988b5139ac1256CAS |

[54]  L. J. Hofseth, S. P. Hussain, G. N. Wogan, C. C. Harris, Free Radic. Biol. Med. 2003, 34, 955.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXislemtro%3D&md5=a75f0d8031b4f67f3231e5eaa70c3758CAS |

[55]  K. D. Kröncke, K. Fehsel, V. Kolb-Bachofen, Nitric Oxide-Biol. Ch. 1997, 1, 107.
         | Crossref | GoogleScholarGoogle Scholar |

[56]  P. Pacher, J. S. Beckman, L. Liaudet, Physiol. Rev. 2007, 87, 315.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXitVagsr8%3D&md5=82b6da454e7422b13520e2ad1d9bc208CAS |

[57]  E. C. Chinje, I. J. Stratford, Essays Biochem. 1997, 32, 61.
         | 1:CAS:528:DyaK1cXktVSrug%3D%3D&md5=c6857dee75c08170f487bdba2937a462CAS |

[58]  G. Melino, F. Bernassola, R. A. Knight, M. T. Corasaniti, G. Nistico, Nature 1997, 388, 432.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXltFGmt7o%3D&md5=3852a1527eb3a11944cc4d0e48328857CAS |

[59]  P. E. da Costa, W. L. Batista, M. F. Curcio, M. S. Moraes, R. E. Borges, P. A. Nascimento, L. R. Travassos, H. P. Monteiro, Redox Rep. 2011, 16, 27.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXnvFemtbw%3D&md5=5d5f67f3abc51c4ddf1c7e71d9c72610CAS |

[60]  S. Grant, W. D. Jarvis, P. S. Swerdlow, A. J. Turner, R. S. Traylor, H. J. Wallace, P. S. Lin, G. R. Pettit, D. A. Gewirtz, Cancer Res. 1992, 52, 6270.
         | 1:CAS:528:DyaK3sXislE%3D&md5=8a6a891445d203b073df5b3baf1fbbe2CAS |

[61]  A. Bal-Price, G. C. Brown, J. Neurochem. 2000, 75, 1455.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXmslGltrw%3D&md5=e144f870b46efebea3f6013b0a504bd3CAS |

[62]  Y. Naito, T. Yoshikawa, Y. Boku, T. Fujii, Y. Masui, Y. Tanaka, N. Fujita, N. Yoshida, M. Kondo, Aliment. Pharmacol. Ther. 2000, 14, 145.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXjtl2jsL0%3D&md5=1dbc58b66eea116844fb57c699c66fe8CAS |

[63]  T. A. Reiter, B. Pang, P. Dedon, B. Demple, J. Biol. Chem. 2006, 281, 36603.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1eltrvL&md5=fee446341476f8c1bf63cae169233240CAS |

[64]  Y. T. Ma, R. Conforti, L. Aymeric, C. Locher, O. Kepp, G. Kroemer, L. Zitvogel, Cancer Metastasis Rev. 2011, 30, 71.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXitlKltLY%3D&md5=cff2d73a8d69af48129ee3ddf134e8cbCAS |

[65]  P. Scaffidi, T. Misteli, M. E. Bianchi, Nature 2002, 418, 191.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XltFGlsro%3D&md5=fa5a790c00a5828a76e8a11fe5c88507CAS |

[66]  L. Apetoh, F. Ghiringhelli, A. Tesniere, M. Obeid, C. Ortiz, A. Criollo, G. Mignot, M. C. Maiuri, E. Ullrich, P. Saulnier, H. Yang, S. Amigorena, B. Ryffel, F. J. Barrat, P. Saftig, F. Levi, R. Lidereau, C. Nogues, J. P. Mira, A. Chompret, V. Joulin, F. Clavel-Chapelon, J. Bourhis, F. Andre, S. Delaloge, T. Tursz, G. Kroemer, L. Zitvogel, Nat. Med. 2007, 13, 1050.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVSgtr3E&md5=c89c607904fec2f982a04ceee1bae834CAS |

[67]  J. M. Fukuto, C. H. Switzer, K. M. Miranda, D. A. Wink, Annu. Rev. Pharmacol. Toxicol. 2005, 45, 335.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXisVWjt7Y%3D&md5=d66c1e1c76f7f6b2e6f6ed6aa96d9c4dCAS |

[68]  J. R. O. Filho, W. C. Silva, J. C. M. Pereira, D. W. Franco, Inorg. Chim. Acta 2006, 359, 2888.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XkvVCru7Y%3D&md5=4a19aa45a92a82df82c20886ddd78cc4CAS |

[69]  M. J. Clarke, Coord. Chem. Rev. 2002, 232, 69.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XntF2ktbg%3D&md5=073fc33bbeb7e5e6a4e9247a3728c8caCAS |

[70]  I. Kostova, Curr. Med. Chem. 2006, 13, 1085.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XkslKqtbs%3D&md5=5b002bc5bd110baca1ed7a4f09557141CAS |

[71]  T. Mosmann, J. Immunol. Methods 1983, 65, 55.
         | Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2c%2FovFSmtw%3D%3D&md5=c578bbb14d23f0a24998c66c84c7b83dCAS |

[72]  T. Paschoalin, A. K. Carmona, E. G. Rodrigues, V. Oliveira, H. P. Monteiro, M. A. Juliano, L. Juliano, L. R. Travassos, Mol. Cancer 2007, 6, 44.
         | Crossref | GoogleScholarGoogle Scholar |

[73]  A. S. Dobroff, E. G. Rodrigues, M. A. Juliano, D. M. Friaca, E. S. Nakayasu, I. C. Almeida, R. A. Mortara, J. F. Jacysyn, G. P. Amarante-Mendes, W. Magliani, S. Conti, L. Polonelli, L. R. Travassos, Translational Oncology 2010, 3, 204.