SpringerLink
Log in

Autophagy in MCF-7 cancer cells induced by copper complexes

  • Original article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Background

Autophagy plays an important role in cancer cells. Targeting autophagy in cancer can provide new opportunities for drug development.

Methods

In this study we tested four Schiff base Cu(II) complexes against human breast cancer cells (MCF-7) and human non-cancerous cells (HEK-293T). We have tested their cytotoxic effect by evaluating IC50 using MTT test. To detect morphological changes of the actin fibers we have used fluorescent microscopy. To determine the type of cell death we used electrophoretic analysis and western blot analysis (protein LC3).

Results

IC50 values of the complexes increased with time of their influence, indicating acquired resistance of MCF-7 to the complexes. Healthy cells HEK-293T were not sensitive to the Cu(II) complexes. Compared with the control cells (cells without Cu(II) complexes) which were without morphological changes of actin fibers, Cu(II) complexes induced condensation and asymmetric conformational changes in actin filaments. To examine the type of cell death induced by the Cu(II) complexes we treated MCF-7 cells with Cu(II) complexes (1, 10, 50 and 100 μmol/L) during a 72 h incubation period. By electrophoresis we have not detected any DNA fragmentation. To determine whether Cu(II) complexes induced autophagy or necrotic cell death we used the western blot analysis. MCF-7 cells influenced with tested Cu(II) complexes produced LC3 protein after their 72 h incubation indicating autophagy in MCF-7 cancer cells.

Conclusions

Tested Schiff base copper (II) complexes have antiproliferative activity against cancer cells but not against healthy cells. They have induced autophagy in the cancer cell line MCF-7.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lowe SW, Lin WA. Apoptosis in cancer. Cancerogenesis 2000;2(3)485–95 1.

    Google Scholar 

  2. Hajrezaie M, Paydar M, Moghadamtousi SZ, Hassandarvish P, Gwaram NS, Zahedifard ME, et al. Schiff base-derived copper (II) complex is a potent inducer of apoptosis in colon cancer cells by activating the intrinsic pathway. Sci World J 2014;2014(2014):12.

    Google Scholar 

  3. Liang C, **a J, Lei D, Li X, Yao Q, Gao J. Synthesis, in vitro and in vivo antitumor activity of symmetrical bis-Schiff base derivatives of isatin. Eur J Med Chem 2014;74:742–50.

    Article  CAS  PubMed  Google Scholar 

  4. Zhong W, Zhu H, Sheng F, Tian Y, Zhou J, Chen Y, et al. Activation of the MAPK11/12/13/14 (p38 MAPK) pathway regulates the transcription of autophagy genes in response to oxidative stress induced by a novel copper complex in HeLa cells. Autophagy 2014;10(7):1285–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Farber E. Programmed cell death: necrosis versus apoptosis. Mod Pathol 1994;7(5):605–9.

    CAS  PubMed  Google Scholar 

  6. Langer V, Gyepesová D, Scholtzová E, Mach P, Kohútová M, Valent A, et al. Crystal and electronic structure of aqua(N-salicylidene-methylester-L-glutamato)Cu(II) monohydrate. Z Kristallogr 2004;219(2004):112–6.

    CAS  Google Scholar 

  7. Langer V, Scholtzová E, Gyepesová D, Kohútová M, Valent A. (N-salicylidene-D, L-glutamato)(2-methylimidazole)copper(II). Acta Cryst 2004;0:129–32.

    Google Scholar 

  8. Langer V, Gyepesová D, Kohútová M, Valent A. Dimeric (isoquinoline)(N-salicylidene-D,L-glutamato)copper(II) ethanol solvate. Acta Cryst 2009; C65:208–10.

    Article  Google Scholar 

  9. Langer V, Mach P, Gyepesová D, Andrezálová L, Kohútová M. X-ray and DFT studies of a mono- and binuclear copper(II) ionic compound containing a Schiff base. Acta Cryst 2012;C68:326–8.

    Google Scholar 

  10. Vyas A, Patitungkho S, Jamadar A, Adsule S, Padhyea S, Ahmad A. ATRA-hydrazonate derivatives and their copper complexes against hormone-dependent (MCF-7), hormone-independent (MDA-MB-231 and BT-20) breast cancer and androgen-independent (PC3) prostate cancer cell lines. Inorg Chem Commun 2012;23:17–20.

    Article  CAS  Google Scholar 

  11. Francisco D, Peddi P, Hair JM, Flood BA, Cecil AM, Kalogerinis PT. Induction and processing of complex DNA damage in human breast cancer cells MCF-7 and nonmalignant MCF-10A cells. Free Radic Biol Med 2009;44(4):558–69.

    Article  Google Scholar 

  12. Santini C, Pellei M, Gandin V, Porchia M, Tisato F, Marzano C. Advances in copper complexes as anticancer agents. Chem Rev 2014;114(1):815–62.

    Article  CAS  PubMed  Google Scholar 

  13. Frias González SE, Anguiano EA, Herrera AM, Calzada DE, Pichardo CO. Cytotoxic, pro-apoptotic, pro-oxidant, and non-genotoxic activities of a novel copper(II) complex against human cervical cancer. Toxicology 2013;314 (1):155–6.

    Article  PubMed  Google Scholar 

  14. Singh R, Jadeja RN, Thounaojam MC, Patel T, Devkar RV, Chakraborty D. Synthesis, DNA binding and antiproliferative activity of ternary copper complexes of moxifloxacin and gatifloxacin against lung cancer cells. Inorg Chem Commun 2012;23:78–84.

    Article  CAS  Google Scholar 

  15. Vyas MV, Jadeja RN, Patel D, Devkar RV, Gupta VK. Effect of ligand substitution in pyrazolone based binary and ternary Cu(II) complexes on DNA binding, protein binding and anti-cancer activity on A549 lung carcinoma cell lines. Polyhedron 2014;80:20–33.

    Article  CAS  Google Scholar 

  16. Wen-jie G, Si-si Y, Ning C, **g G, Qiu-yun Q. ROS-mediated autophagy was involved in cancer cell death induced by novel copper(II) complex. Exp Toxicol Pathol 2010;62(5):577–82.

    Article  Google Scholar 

  17. Bhumika T, Noble A, Creaven BS, Walsh M, Kavanagh K, Egan DA. Apoptotic cell death: a possible key event in mediating the in vitro anti-proliferative effect of a novel copper(II) complex, [Cu(4-Mecdoa)(phen)2] (phen = phenanthroline, 4-Mecdoa = 4-methylcoumarin-6,7-dioxactetate), in human malignant cancer cells. Eur J Pharmacol 2007;569(1–2):16–8.

    Google Scholar 

  18. Milacic V, Chen D, Giovagnini L, Diez A, Fregona D, Dou QP. Pyrrolidine dithiocarbamate-zinc(II) and -copper(II) complexes induce apoptosis in tumor cells by inhibiting the proteasomal activity. Toxicol Appl Pharmacol 2008;231(1):24–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. De Vizcaya-Ruiz A, Rivero-Muller A, Ruiz-Ramirez L, Kass GE, Kelland LR, Orr RM, et al. Induction of apoptosis by a novel copper-based anticancer compound, casiopeina II, in L1210 murine leukaemia and CH1 human ovarian carcinoma cells. Toxicol In Vitro 2000;14(1):1–5.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic

    Katarína Koňariková, Georgios A. Perdikaris, Lucia Andrezálová, Lucia Laubertová & Ingrid Žitňanová

  2. Institute of Medical Biology and Genetics, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic

    Helena Gbelcová & Soňa Režnáková

  3. Department of Biochemistry and Microbiology, Faculty of Food Biochemical Technology, Institute of Chemical Technology, Technicka 5, Prague, 166 28, Czech Republic

    Martin Švéda & Tomáš Ruml

Authors
  1. Katarína Koňariková
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Georgios A. Perdikaris
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Helena Gbelcová
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lucia Andrezálová
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Martin Švéda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomáš Ruml
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lucia Laubertová
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Soňa Režnáková
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ingrid Žitňanová
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ingrid Žitňanová.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Koňariková, K., Perdikaris, G.A., Gbelcová, H. et al. Autophagy in MCF-7 cancer cells induced by copper complexes. Pharmacol. Rep 68, 1221–1224 (2016). https://doi.org/10.1016/j.pharep.2016.07.011

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.pharep.2016.07.011

Keywords

Search

Navigation