Skip to main content
SpringerLink
Log in

The mitochondrial apoptotic pathway is induced by Cu(II) antineoplastic compounds (Casiopeínas®) in SK-N-SH neuroblastoma cells after short exposure times

  • Published:
BioMetals Aims and scope Submit manuscript

Abstract

The family of Copper(II) coordination compounds Casiopeínas® (Cas) has shown antiproliferative activity in several tumour lines by oxidative cellular damage and mitochondrial dysfunction that lead to cell death through apoptotic pathways. The goal of this work is looking for the functional mechanism of CasIIgly, CasIIIia and CasIIIEa in neuroblastoma metastatic cell line SK-N-SH, a paediatric extra-cranial tumour which is refractory to several anti-carcinogenic agents. All Cas have shown higher antiproliferative activity than cisplatin (IC50 = 123 μM) with IC50 values of 18, 22 and 63 µM for CasIIgly, CasIIIEa and CasIIIia, respectively. At low concentrations and early times (4 h), these compounds cause a disruption of the mitochondrial transmembrane potential (Δψm). Concomitantly, an important depletion of intracellular glutathione and an increase of reactive oxygen species (ROS) hydrogen peroxide and radical superoxide were observed. On the other side, the lower cytotoxic effect of Casiopeínas on cultures of human peripheral blood lymphocytes (IC50 CasIIgly  = 1720 µM, IC50 CasIIIEa  = 3860 µM and IC50 CasIIIia  = 4700 µM) show the selectivity of these compounds over the tumour cells compared with the non-transformed cells. Chemically, glutathione (GSH) interacts with Casiopeínas® through the coordination of sulphur atom to the metal centre, process which facilitates the electron transfer to get Cu(I), GSSG and the posterior production of ROS. Additionally, the molecular structure of CasIIIia as nitrate is reported. These results have shown that the anticarcinogenic activity of Casiopeínas® on neuroblastoma SK-N-SH is through mitochondrial apoptosis due to the enhanced pro-oxidant environment promoted by the presence of the coordination copper compounds.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Scheme 1
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Agilent (2013) CrysAlis PRO and CrysAlis RED. Agilent Technologies, Yarnton

    Google Scholar 

  • Alemón-Medina R, Breña-Valle M, Muñoz-Sánchez JL, Gracia-Mora I, Ruiz-Azuara L (2007) Induction of oxidative damage by copper-based antineoplastic drugs (Casiopeínas®). Cancer Chemother Pharmacol 60:219–228. doi:10.1007/s00280-006-0364-9

    Article  PubMed  Google Scholar 

  • Alemón-Medina R, Muñoz-Sánchez JL, Ruiz-Azuara L, Gracia-Mora I (2008) Casiopeína IIgly induced cytotoxicity to HeLa cells depletes the levels of reduced glutathione and is prevented by dimethyl sulfoxide. Toxicol Vitro 22:710–715. doi:10.1016/j.tiv.2007.11.011

    Article  Google Scholar 

  • Alemón-Medina R, Bravo-Gómez ME, Gracia-Mora MI, Ruiz-Azuara L (2011) Comparison between the antiproliferative effect and intracellular glutathione depletion induced by Casiopeína IIgly and cisplatin in murine melanoma B16 cells. Toxicol Vitro 25:868–873. doi:10.1016/j.tiv.2011.02.007

    Article  Google Scholar 

  • Becco L, Rodríguez A, Bravo ME, Prieto MJ, Ruiz-Azuara L, Garat B, Moreno V, Gambino D (2012) New achievements on biological aspects of copper complexes Casiopeínas®: interaction with DNA and proteins and anti-Trypanosoma cruzi activity. J Inorg Biochem 109:49–56. doi:10.1016/j.jinorgbio.2012.01.010

    Article  CAS  PubMed  Google Scholar 

  • Becco L, García-Ramos JC, Azuara L, Gambino D, Garat B (2014) Analysis of the DNA interaction of copper compounds belonging to the Casiopeínas® antitumoral series. Biol Trace Elem Res 161:210–215. doi:10.1007/s12011-014-0098-1

    Article  CAS  PubMed  Google Scholar 

  • Bertrand B, Casini A (2014) A golden future in medicinal inorganic chemistry: the promise of anticancer gold organometallic compounds. Dalton Trans 43:4209–4219. doi:10.1039/C3DT52524D

    Article  CAS  PubMed  Google Scholar 

  • Biasutto L, Dong LF, Zoratti M, Neuzil J (2010) Mitochondrially targeted anti-cancer agents. Mitochondrion 10:670–681. doi:10.1016/j.mito.2010.06.004

    Article  CAS  PubMed  Google Scholar 

  • Bica L, Meyerowitz J, Parker SJ, Caragounis A, Du T, Paterson BM, Barnham KJ, Crouch PJ, White AR, Donelly PS (2011) Cell cycle arrest in cultured neuroblastoma cells exposed to a bis(thiosemicarbazonato) metal complex. Biometals 24:117–133. doi:10.1007/s10534-010-9380-7

    Article  CAS  PubMed  Google Scholar 

  • Biedler JL, Helson L, Barbara A (1973) Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Res 33(2643):2652

    Google Scholar 

  • Bielski BHJ, Cabelli DE, Arudi RL, Ross AB (1985) Reactivity of HO2/O2- radicals in aqueous solution. J Phys Chem Ref Data 14:1041–1100. https://srd.nist.gov/JPCRD/jpcrd285.pdf

  • Bravo-Gómez ME, García-Ramos JC, Gracia-Mora I, Ruiz-Azuara L (2009) Antiproliferative activity and QSAR study of copper(II) mixed chelate [Cu(N–N) (acetylacetonato)]NO3 and [Cu(N–N) (glycinato)]NO3 complexes, (Casiopeínas®). J Inorg Biochem 103:299–309. doi:10.1016/j.jinorgbio.2008.10.006

    Article  PubMed  Google Scholar 

  • Bravo-Gómez ME, Dávila-Manzanilla S, Flood-Garibay J, Muciño-Hernández MA, Mendoza A, García-Ramos JC, Moreno-Esparza R, Ruiz-Azuara L (2012) Secondary ligand effects on the cytotoxicity of several Casiopeína’s Group II compounds. J Mex Chem Soc 56:85–92

    Google Scholar 

  • Carvallo-Chaigneau F, Gómez-Ruiz C, Rodríguez-Aguilera E, Macías-Rosales L, Cortés-Barberena E, Cedillo-Peláez C, Gracia-Mora I, Ruiz-Azuara L, Madrid-Marina V, Constantino-Casas F (2008) Casiopeina III-ia induces apoptosis in HCT-15 cells in vitro through caspase-dependent mechanisms and has antitumor effect in vivo. Biometals 21:17–28. doi:10.1007/s10534-007-9089-4

    Article  CAS  PubMed  Google Scholar 

  • Chao MP, Majeti R, Weissman IL (2011) Programmed cell removal: a new obstacle in the road to developing cancer. Nat Rev Cancer 12:58–67. doi:10.1038/nrc3171

    PubMed  Google Scholar 

  • Combaret V, Boyault S, Lacono L, Berejon S, Rousseau R, Puisieux A (2008) Effect of bortezomib on human neuroblastoma: analysis of molecular mechanisms involved in cytotoxicity. Mol Cancer 7:50. doi:10.1186/1476-4598-7-50

    Article  PubMed  PubMed Central  Google Scholar 

  • De Vizcaya-Ruiz A, Rivero-Müller A, Ruiz-Ramírez L, Kass GE, Kelland LR, Orr RM, Dobrota M (2000) Induction of apoptosis by a novel copper-based anticancer compound, casiopeina II, in L1210 murine leukaemia and CH1 human ovarian carcinoma cells. Toxicol Vitro 14:1–5. doi:10.1016/S0887-2333(99)00082-X

    Article  Google Scholar 

  • Derenzini M, Pession A, Farabegoli F, Treré D, Badiali M, Dehan P (1989) Relationship between interphasic nucleolar organizer regions and growth rate in two neuroblastoma cell lines. Am J Pathol 134:925–932

    CAS  PubMed  PubMed Central  Google Scholar 

  • Downes JM, Whelan J, Bosnich B (1981) Biological analogs. Spectroscopic characteristics of mercapto- and disulfide-copper(II) coordination in relation to type I proteins. Inorg Chem 20:1081–1086. doi:10.1021/ic50218a025

    Article  CAS  Google Scholar 

  • Dukes CE, Masina F (1949) Classification of epithelial tumours of the bladder. Br J Urol 21:273–295. doi:10.1111/j.1464-410X.1949.tb10787.x

    Article  CAS  PubMed  Google Scholar 

  • Farrugia L (1999) WinGX suite for small-molecule single-crystal crystallography. J Appl Crystallogr 32:837–838. doi:10.1107/S0021889899003039

    Article  CAS  Google Scholar 

  • Galindo-Murillo R, Ruíz-Azuara L, Moreno-Esparza R, Cortés-Guzmán F (2012) Molecular recognition between DNA and a copper-based anticancer complex. Phys Chem Chem Phys 14:15539–15546. doi:10.1039/C2CP42185B

    Article  CAS  PubMed  Google Scholar 

  • Galindo-Murillo R, García-Ramos JC, Ruiz-Azuara L, Cheatham TE III, Cortés-Guzmán F (2015) Intercalation processes of copper complexes in DNA. Nucleic Acids Res 43:5364–5376. doi:10.1093/nar/gkv467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • García-Ramos JC, Toledano-Magaña Y, Talavera-Contreras LG, Flores-Alamo M, Ramírez-Delgado V, Morales-León E, Ortiz-Frade L, Gutiérrez AG, Vázquez-Aguirre A, Mejía C, Carrero JC, Laclette JP, Moreno-Esparza R, Ruiz-Azuara L (2012) Potential cytotoxic and amoebicide activity of first row transition metal compounds with 2,9-bis-(2′,5′-diazahexanyl)-1,10-phenanthroline (L1). Dalton Trans 41:10164–10174. doi:10.1039/C2DT30224A

    Article  PubMed  Google Scholar 

  • Goldstein S, Czapski G (1983) Mechanisms of the dismutation of superoxide catalyzed by the copper(II) phenanthroline complex and of the oxidation of the copper(I) phenanthroline complex by oxygen in aqueous solution. J Am Chem Soc 105:7276–7280. doi:10.1021/ja00363a012

    Article  CAS  Google Scholar 

  • Guan S, Zhao Y, Lu J, Yu Y, Sun W, Mao X, Chen Z, Xu X, Pan J, Sun S, Yang J (2016) Second-generation proteasome inhibitor carfilzomib sensitizes neuroblastoma cells to doxorubicin-induced apoptosis. Oncotarget. doi:10.18632/oncotarget.12427

    Google Scholar 

  • Gutiérrez AG, Vázquez-Aguirre A, García-Ramos JC, Flores-Alamo M, Hernández-Lemus E, Ruiz-Azuara L, Mejía C (2013) Copper(II) mixed chelate compounds induce apoptosis through reactive oxygen species in neuroblastoma cell line CHP-212. J Inorg Biochem 126:17–25. doi:10.1016/j.jinorgbio.2013.05.001

    Article  PubMed  Google Scholar 

  • Haglund C, Åleskog A, Nygren P, Gullbo J, Höglund M, Wickström M, Larsson R, Lindhagen E (2012) In vitro evaluation of clinical activity and toxicity of anticancer drugs using tumor cells from patients and cells representing normal tissues. Cancer Chemother Pharmacol 69:697–707. doi:10.1007/s00280-011-1746-1

    Article  CAS  PubMed  Google Scholar 

  • Hernández-Lemus E, Gutiérrez AG, Vázquez-Aguirre A, Palma-Tirado ML, Ruiz-Azuara L, Mejía C (2013) Analysis of apoptotic and autophagic pathways in neuroblastoma by treatment with copper compounds. Neuroblastoma. InTech, Croatia, pp 145–161

    Google Scholar 

  • Ireland CM, Pittman SM, Jones SL, Harnett PR (1994) Establishment of an in vitro model for cisplatin resistance in human neuroblastoma cell lines. Anticancer Res 14:2397–2403

    CAS  PubMed  Google Scholar 

  • Ishikawa T, Wrigth CD, Ishizuka H (1994) GS-X pump is functionally overexpressed in cis-diamminedichloroplatinum(II)-resistant human leukemia HL-60 cells and down-regulated by cell differentiation. J Biol Chem 269:29085–29093

    CAS  PubMed  Google Scholar 

  • Kachadourian R, Brechbuhl HM, Ruiz-Azuara L, Gracia-Mora I, Day BJ (2010) Casiopeína IIgly-induced oxidative stress and mitochondrial dysfunction in human lung cancer A549 and H157 cells. Toxicology 268:176–183. doi:10.1016/j.tox.2009.12.010

    Article  CAS  PubMed  Google Scholar 

  • Kamencic H, Lyon A, Paterson PG, Juurlink BHJ (2000) Monochlorobimane fluorometric method to measure tissue glutathione. Anal Biochem 286:35–37. doi:10.1006/abio.2000.4765

    Article  CAS  PubMed  Google Scholar 

  • Leal-García M, García-Ortuño L, Ruiz-Azuara L, Gracia-Mora I, Luna-Delvillar J, Sumano H (2007) Assessment of acute respiratory and cardiovascular toxicity of Casiopeinas in anaesthetized dogs. Basic Clin Pharmacol Toxicol 101:151–158. doi:10.1111/j.1742-7843.2007.00038.x

    Article  PubMed  Google Scholar 

  • Li LC, Sheng JR, Mulherkar N, Prabhakar BS, Meriggioli MN (2008) Regulation of apoptosis and Caspase-8 expression in neuroblastoma cells by isoforms of the IG20 gene. Cancer Res 15:7352–7361. doi:10.1158/0008-5472.CAN-07-6311

    Article  Google Scholar 

  • Maris JM (2010) Recent advances in neuroblastoma. New Engl J Med 10:2202–2211. doi:10.1056/NEJMra0804577

    Article  Google Scholar 

  • Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK, Swift P, Shimada H, Black CT, Brodeur GM, Gerbing RB, Reynolds CP (1999) Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-Retinoic acid. N Engl J Med 341:1165–1173. doi:10.1056/NEJM199910143411601

    Article  CAS  PubMed  Google Scholar 

  • Mejía C, Ruiz-Azuara L (2008) Casiopeinas IIgly and IIIia induce apoptosis in medulloblastoma cells. Pathol Oncol Res 14:467–472. doi:10.1007/s12253-008-9060-x

    Article  PubMed  Google Scholar 

  • Modica-Napolitano JS, Keshav K (2004) Mitochondrial dysfunction in cancer. Mitochondrion 4:755–762. doi:10.1016/j.mito.2004.07.027

    Article  CAS  PubMed  Google Scholar 

  • Muhammad N, Guo Z (2014) Metal-based anticancer chemotherapeutic agents. Curr Opin Chem Biol 19:144–153. doi:10.1016/j.cbpa.2014.02.003

    Article  CAS  PubMed  Google Scholar 

  • National Cancer Institute (2015) PDQ neuroblastoma treatment. National Cancer Institute, Bethesda. Date last modified 03/22/2013. http://www.cancer.org/cancer/neuroblastoma/detailedguide/neuroblastoma-survival-rates. Accessed 25 Nov, 2015

  • Paterson BM, Donelly PS (2011) Copper complexes of bis(thiosemicarbazones): from chemotherapeutics to diagnostic and therapeutic radiopharmaceuticals. Chem Soc Rev 40:3005–3018. doi:10.1039/C0CS00215A

    Article  CAS  PubMed  Google Scholar 

  • Patterson MK Jr (1979) Measurement of growth and viability of cells in culture. Method Enzymol 58:141–152

    Article  Google Scholar 

  • Rivero-Müller A, De Vizcaya-Ruiz A, Plant N, Ruiz L, Dobrota M (2007) Mixed chelate copper complex, Casiopeina IIgly, binds and degrades nucleic acids: a mechanism of cytotoxicity. Chem Biol Interact 165:189–199. doi:10.1016/j.cbi.2006.12.002

    Article  PubMed  Google Scholar 

  • Ruggiero A, Trombatore G, Triarico S, Arena R, Ferrara P, Scalzone M, Pierri F, Riccardi R (2013) Platinum compounds in children with cancer: toxicity and clinical management. Anticancer Drugs 24:1007–1019. doi:10.1097/CAD.0b013e3283650bda

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Azuara L, Patente, Enero 26 (1994) no. 172967; SECOFI 18802. PI (1990) Patente Dic.9 (1993) no. 172248; US Patent Ap 21 (1992) Number 5, 107, 005. Re35, 458, Feb. 18 (1997); U. S. Patent Pat. No. 5,576,326. Nov. 19 (1996) [®Trade Mark: Casiopeína. Reg. 407543 SECOFI (1992), renewal (2002), (2012)]

  • Ruiz-Azuara L (1996) Copper amino acidate diimine nitrate compounds and their methyl derivatives and a process for preparing them. Ap. N. 07/628,628; 5,576,326

  • Ruiz-Azuara L (1997) Process to obtain new mixed copper aminoacidate complexes from phenylatephenanthroline to be used as anticancerigenic agents. Ap N. 07/628,843; RE 35,458, Feb. 18, 1992.

  • Ruiz-Azuara L, Bravo-Gómez ME (2010) Copper compounds in cancer chemotherapy. Curr Med Chem 17:3606–3615. doi:10.2174/092986710793213751

    Article  CAS  PubMed  Google Scholar 

  • Ryan J, Tiunan A, Fay J, Bryan K, Meehan M, Greevey L, Lynch J, Bray IM, O’Meara A, Davidoff AM, Stallings RL (2012) MicroRNA-204 increases sensitivity of neuroblastoma cells to cisplatin and is associated with a favourable clinical outcome. Br J Cancer 107:967–976. doi:10.1038/bjc.2012.356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santini C, Pellei M, Gandin V, Porchia M, Tisato F, Marzano C (2014) Advances in copper complexes as anticancer agents. Chem Rev 114:815–862. doi:10.1021/cr400135x

    Article  CAS  PubMed  Google Scholar 

  • Sava G, Jaouen G, Hillard EA, Bergamo A (2012) Targeted therapy vs. DNA-adduct formation-guided design: thoughts about the future of metal-based anticancer drugs. Dalton Trans 41:8226–8234. doi:10.1039/C2DT30075C

    Article  CAS  PubMed  Google Scholar 

  • Schafer FQ, Buetner GR (2001) Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Rad Biol Med 30:1191–1212. doi:10.1016/S0891-5849(01)00480-4

    Article  CAS  PubMed  Google Scholar 

  • Serment-Guerrero J, Cano-Sánchez P, Reyes-Pérez E, Velázquez-García F, Bravo-Gómez ME, Ruiz-Azuara L (2011) Genotoxicity of the copper antineoplastic coordination complexes casiopeinas. Toxicol Vitro 25:1376–1384. doi:10.1016/j.tiv.2011.05.008

    Article  CAS  Google Scholar 

  • Sheldrick GM (2008) A short history of SHELX. Acta Cryst Sect A Found Crystallogr 64:112–122. doi:10.1107/s0108767307043930

    Article  CAS  Google Scholar 

  • Sirri V, Pession A, Treré D, Montaniou L, Derenzini M (1995) Proportionally constant quantitative transmission of nucleolin and protein B23 in cycling cancer cells. Clin Mol Pathol 48:M264–M268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tovar-Tovar A, Ruiz-Ramírez L, Campero A, Romerosa A, Moreno-Esparza R, Rosales-Hoz J (2004) Structural and reactivity studies on 4,4′-dimethyl-2,2′-bipyridine acetylacetonate copper(II) nitrate (CASIOPEINA III-ia®) with methionine, by UV–visible and EPR techniques. J Inorg Biochem 98:1045–1053. doi:10.1016/j.jinorgbio.2004.02.023

    Article  CAS  Google Scholar 

  • Trejo-Solís C, Palencia G, Zúñiga S, Rodríguez-Ropón A, Osorio-Rico L, Sánchez L, Gracia-Mora I, Márquez-Rosado L, Sánchez A, Moreno-García ME, Cruz A, Bravo-Gómez ME, Ruiz-Ramírez L, Rodríguez-Enríquez S, Sotelo J (2005) Cas IIgly induces apoptosis in glioma C6 cells in vitro and in vivo through caspase-dependent and caspase-independent mechanisms. Neoplasia 7:563–574. doi:10.1593/neo.04607

    Article  PubMed  PubMed Central  Google Scholar 

  • Trejo-Solís C, Jiménez-Farfán D, Rodríguez-Enríquez S, Fernández-Valverde F, Cruz-Salgado A, Ruiz-Azuara L, Sotelo J (2012) Copper compound induces autophagy and apoptosis of glioma cells by reactive oxygen species and jnk activation. BMC Cancer 12:156. doi:10.1186/1471-2407-12-156

    Article  PubMed  PubMed Central  Google Scholar 

  • Valencia-Cruz AI, Uribe-Figueroa LI, Galindo-Murillo R, Baca-López K, Gutiérrez AG, Vázquez-Aguirre A, Ruiz-Azuara L, Hernández-Lemus E, Mejía C (2013) Whole genome gene expression analysis reveals casiopeína-induced apoptosis pathways. PLoS ONE 8:e54664. doi:10.1371/journal.pone.0054664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vértiz G, García-Ortuño LE, Bernal JP, Bravo-Gómez ME, Lounejeva E, Huerta A, Ruiz-Azuara L (2012) Pharmacokinetics and hematotoxicity of a novel copper-based anticancer agent: casiopeina III-Ea, after a single intravenous dose in rats. Fundam Clin Pharmacol 28:78–87. doi:10.1111/j.1472-8206.2012.01075.x

    Article  PubMed  Google Scholar 

  • Vo KT, Matthay KK, Neuhaus J, London WB, Hero B, Ambros PF, Nakagawara A, Miniati D, Wheeler K, Pearson AD, Cohn SL, DuBois SG (2014) Clinical, biologic, and prognostic differences on the basis of primary tumor site in neuroblastoma: a report from the international neuroblastoma risk group project. J Clin Oncol 32:3169–3176. doi:10.1200/JCO.2014.56.1621

    Article  PubMed  PubMed Central  Google Scholar 

  • Weil JA, Bolton JR, Wertz JE (1994) Electron spin resonance: elementary theory and practical applications. Wiley, New York

    Google Scholar 

  • Yu F, Zhu X, Feng C, Wang T, Hong Q, Liu Z, Tang S (2011) Proteomics-based identification of spontaneous regression-associated proteins in neuroblastoma. J Peditr Surg 46:1948–1955. doi:10.1016/j.jpedsurg.2011.06.024

    Article  CAS  Google Scholar 

  • Zhang H, Thomas R, Oupicky D, Peng F (2008) Synthesis and characterization of new copper thiosemicarbazone complexes with an ONNS quadridentate system: cell growth inhibition, S-phase cell cycle arrest and proapoptotic activities on cisplatin-resistant neuroblastoma cells. J Biol Inorg Chem 13:47–55. doi:10.1007/s00775-007-0299-6

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Wei JS, Li SQ, Badgett TC, Song YK, Agarwal S, Coarfa C, Tolman C, Hurd L, Liao H, He J, Wen X, Liu Z, Thiele CJ, Westermann F, Asgharzadeh S, Seeger RC, Maris JM, Guidry Auvil JM, Smith MA, Kolaczyk ED, Shohet J, Khan J (2016) MYCN controls an alternative RNA splicing program in high-risk metastatic neuroblastoma. Cancer Lett 371(2):214–224. doi:10.1016/j.canlet.2015.11.045

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported with Grants from PAPIIT-UNAM 204511 and 218013, CONACYT 179119, ICyTDF-PIN VII-32. JCGR and YTM are grateful to DGAPA for postdoctoral Grant. AGG thanks CONACyT for the scholarship Grant. Authors acknowledge Gonzalo Acero for technical support.

Author information

Author notes

    Authors and Affiliations

    1. Laboratorio de Química Inorgánica Medicinal, Facultad de Química, Universidad Nacional Autónoma de México, Av. Universidad 3000, Z.P. 04510, Mexico City, Mexico

      Juan Carlos García-Ramos, Yanis Toledano-Magaña, Ana Luisa Alonso-Sáenz, Marcos Flores-Alamo & Lena Ruiz-Azuara

    2. Instituto de Química, Universidad Nacional Autónoma de México, Av. Universidad 3000, Z.P. 04510, Mexico City, Mexico

      Juan Carlos García-Ramos & Virginia Gómez-Vidales

    3. Centro de Investigaciones Biomédicas, Universidad Veracruzana, Jalapa, Veracruz, Mexico

      Anllely Grizett Gutiérrez

    4. Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Avenida de las Ciencias S/N Juriquilla, Delegación Santa Rosa Jáuregui, C.P. 76230, Querétaro, Mexico

      Adriana Vázquez-Aguirre & Carmen Mejía

    Authors
    1. Juan Carlos García-Ramos
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Anllely Grizett Gutiérrez
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Adriana Vázquez-Aguirre
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Yanis Toledano-Magaña
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Ana Luisa Alonso-Sáenz
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Virginia Gómez-Vidales
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Marcos Flores-Alamo
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Carmen Mejía
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Lena Ruiz-Azuara
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Carmen Mejía or Lena Ruiz-Azuara.

    Additional information

    Juan Carlos García-Ramos and Anllely Grizett Gutiérrez have contributed equally to the work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    García-Ramos, J.C., Gutiérrez, A.G., Vázquez-Aguirre, A. et al. The mitochondrial apoptotic pathway is induced by Cu(II) antineoplastic compounds (Casiopeínas®) in SK-N-SH neuroblastoma cells after short exposure times. Biometals 30, 43–58 (2017). https://doi.org/10.1007/s10534-016-9983-8

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10534-016-9983-8

    Keywords

    Search

    Navigation