BioMetals

, Volume 31, Issue 2, pp 189–202 | Cite as

The ability of silver(I) thiocyanate 4-methoxyphenyl phosphine to induce apoptotic cell death in esophageal cancer cells is correlated to mitochondrial perturbations

Article

Abstract

First generation silver(I) phosphines have garnered much interest due to their vast structural diversity and promising anticancer activity. Increasing incidences of cancer, side-effects to chemotherapeutic agents and redevelopment of tumors due to resistance prompts the exploration of alternative compounds showing anticancer activity. This study revealed the effective induction of cell death by a silver(I) thiocyanate 4-methoxyphenyl phosphine complex in a malignant esophageal cell line. Apoptotic cell death was confirmed in treated cells. Moreover, mitochondrial targeting via the intrinsic cell death pathway was evident due to low levels of ATP, altered ROS activity, mitochondrial membrane depolarization, cytochrome c release and caspase-9 cleavage. The complex displayed low cytotoxicity towards two human non-malignant, skin and kidney, cell lines. The findings reported herein give further insight into the selective targeting of silver(I) phosphines and support our belief that this complex shows great promise as an effective chemotherapeutic drug.

Keywords

Cancer Anticancer drugs Apoptosis Mitochondria Silver(I) phosphine 

Abbreviations

Δψm

Mitochondrial membrane potential

Apaf-1

Apoptosis protease activating factor-1

CCCP

Carbonyl cyanide 3-chlorophenylhydrazone

CDDP

Cis-diamine-dichloro platinum (cisplatin)

Cyt c

Cytochrome c

DMSO

Dimethyl sulfoxide

FITC

Fluorescein isothiocyanate

IC50

Half maximal inhibitory concentration

LMS

Leiomyosarcoma cells

MOMP

Mitochondrial outer membrane permeabilization

PARP

Poly (ADP-ribose) polymerase

PI

Propidium iodide

PS

Phosphatidylserine

ROS

Reactive oxygen species

Notes

Acknowledgments

The authors gratefully acknowledge financial assistance from the University of Johannesburg. The Spectrum facility at the University of Johannesburg is acknowledged for the use of the NMR spectrometer and FACSAria flow cytometer.

References

  1. Acs AC (2010) Cancer Facts & Figures 2010. American Cancer Society, Atlanta. http://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2010.html. Accessed May 18, 2017
  2. Berners-Price SJ, Sadler PJ (1988) Phosphines and metal phosphine complexes: relationship of chemistry to anticancer and other biological activity. Struct Bond 70:27–102CrossRefGoogle Scholar
  3. Berners-Price SJ, Mirabelli CK, Johnson RK, Mattern MR, McCabe FL, Faucette LF, Sung CM, Mong SM, Sadler PJ, Crooke ST (1986) In vivo antitumor activity and in vitro cytotoxic properties of bis [1, 2-bis (diphenylphosphino) ethane] gold (I) chloride. Cancer Res 46(11):5486–5493PubMedGoogle Scholar
  4. Borst P, Rottenberg S, Jonkers J (2008) How do real tumors become resistant to cisplatin? Cell Cycle 7(10):1353–1359CrossRefPubMedGoogle Scholar
  5. Brandys MC, Puddephatt RJ (2002) Polymeric complexes of silver(I) with diphosphine ligands: self-assembly of a puckered sheet network structure. J Am Chem Soc 124(15):3946–3950CrossRefPubMedGoogle Scholar
  6. Cain K, Bratton SB, Cohen GM (2002) The Apaf-1 apoptosome: a large caspase-activating complex. Biochimie 84:203–214CrossRefPubMedGoogle Scholar
  7. Engelbrecht Z, Potgieter K, Mpela Z, Malgas-Enus R, Meijboom R, Cronjé MJ (2017) A comparison of the toxicity of mono, bis, tris and tetrakis phosphino silver complexes on SNO esophageal cancer cells. Anticancer Agents Med Chem. doi: https://doi.org/10.2174/1871520617666170522123742 PubMedGoogle Scholar
  8. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917CrossRefPubMedGoogle Scholar
  9. Ferreira E, Munyaneza A, Omondi B, Meijboom R, Cronjé MJ (2015) The effect of 1:2 Ag (I) thiocyanate complexes in MCF-7 breast cancer cells. Biometals 28(4):765–781CrossRefPubMedGoogle Scholar
  10. Gakunga R, Parkin DM (2015) Cancer registries in Africa 2014: a survey of operational features and uses in cancer control planning. Int J Cancer 137(9):2045–2052CrossRefPubMedGoogle Scholar
  11. Human Z, Munyaneza A, Omondi B, Meijboom R, Cronjé MJ (2015) The induction of cell death by phosphine silver(I) thiocyanate complexes in SNO-esophageal cancer cells. Biometals 28(1):219–228CrossRefPubMedGoogle Scholar
  12. Human-Engelbrecht Z, Meijboom R, Cronjé MJ (2017) Apoptosis-inducing ability of silver(I) cyanide-phosphines useful for anti-cancer studies. Cytotechnology 69(4):591–600CrossRefPubMedGoogle Scholar
  13. Johnstone RW, Lowe SW, Ruefli AA (2002) Apoptosis: a link between cancer genetics and chemotherapy. Cell 108:153–164CrossRefPubMedGoogle Scholar
  14. Kelland LR, Mistry P, Abel G, Loh SY, O’Neil CF, Murrer BA, Harrap KR (1992) Mechanism-related circumvention of acquired cis-diamminedichloroplatinum (II) resistance using two pairs of human ovarian carcinoma cell lines by ammine/amine platinum (IV) dicarboxylates. Cancer Res 52:3857–3864PubMedGoogle Scholar
  15. Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257CrossRefPubMedPubMedCentralGoogle Scholar
  16. Kriel FH, Coates J (2012) Synthesis and antitumour activity of gold(I) and silver(I) complexes of hydrazine-bridged diphosphine ligands. S Afr J Chem 65:271–279Google Scholar
  17. Lee KB, Wang D, Lippard SJ, Sharp PA (2002) Transcription-coupled and DNA damage-dependent ubiquitination of RNA polymerase II in vitro. Proc Natl Acad Sci 99:4239–4244CrossRefPubMedPubMedCentralGoogle Scholar
  18. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479–489CrossRefPubMedGoogle Scholar
  19. Liu JJ, Galettis P, Farr A, Maharaj L, Samarasinha H, McGechan A, Baguley BC, Bowen RJ, Berners-Price SJ, McKeage MJ (2008) In vitro antitumour and hepatotoxicity profiles of Au(I) and Ag (I) bidentate pyridyl phosphine complexes and relationships to cellular uptake. J Inorg Biochem 102:303–310CrossRefPubMedGoogle Scholar
  20. McKeage MJ, Papathanasiou P, Salem G, Sjaarda A, Swiegers GF, Waring P, Wild SB (1998) Antitumor activity of gold(I), silver(I) and copper(I) complexes containing chiral tertiary phosphines. Met Based Drugs 5(4):217–223CrossRefPubMedPubMedCentralGoogle Scholar
  21. McKeage MJ, Berners-Price SJ, Galettis P, Bowen RJ, Brouwer W, Ding L, Zhuang L, Baguley BC (2000) Role of lipophilicity in determining cellular uptake and antitumour activity of gold phosphine complexes. Cancer Chemother Pharmacol 46(5):343–350CrossRefPubMedGoogle Scholar
  22. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417(1):1–13CrossRefPubMedGoogle Scholar
  23. Ott M, Robertson JD, Gogvadze V, Zhivotovsky B, Orrenius S (2002) Cytochrome c release from mitochondria proceeds by a two-step process. Proc Natl Acad Sci 99(3):1259–1263CrossRefPubMedPubMedCentralGoogle Scholar
  24. Potgieter K, Cronjé MJ, Meijboom R (2015) Synthesis and characterisation of silver(I) benzyldiphenylphosphine complexes: towards the biological evaluation on SNO cells. Inorg Chim Acta 437:195–200CrossRefGoogle Scholar
  25. Poyraz M, Banti CN, Kourkoumelis N, Dokorou V, Manos MJ, Simčič M, Golič-Grdadolnik S, Mavromoustakos T, Giannoulis AD, Verginadis II, Charalabopoulos K, Hadjikakou SK (2011) Synthesis, structural characterization and biological studies of novel mixed ligand Ag (I) complexes with triphenylphosphine and aspirin or salicylic acid. Inorg Chim Acta 375(1):114–121CrossRefGoogle Scholar
  26. Rackham O, Nichols SJ, Leedman PJ, Berners-Price SJ, Filipovska A (2007) A gold (I) phosphine complex selectively induces apoptosis in breast cancer cells: implications for anticancer therapeutics targeted to mitochondria. Biochem Pharmacol 74(7):992–1002CrossRefPubMedGoogle Scholar
  27. Rafique S, Idrees M, Nasim A, Akbar H, Athar A (2010) Transition metal complexes as potential therapeutic agents. Biotechnol Mol Biol Rev 5:38–45Google Scholar
  28. Riedl SJ, Shi Y (2004) Molecular mechanisms of caspase regulation during apoptosis. Mol Cell Biol 5:897–907Google Scholar
  29. Rodriguez J, Lazebnik Y (1999) Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev 13:3179–3184CrossRefPubMedPubMedCentralGoogle Scholar
  30. Ross MF, Kelso GF, Blaikie FH, James AM, Cochemé HM, Filipovska A, Da Ros T, Hurd TR, Smith RA, Murphy MP (2005) Lipophilic triphenylphosphonium cations as tools in mitochondrial bioenergetics and free radical biology. Biochemistry 70(2):222–230PubMedGoogle Scholar
  31. Segapelo TV, Guzei IA, Spencer LC, Van Zyl WE, Darkwa J (2009) Pyrazolylmethyl) pyridine platinum (II) and gold (III) complexes: synthesis, structures and evaluation as anticancer agents. Inorg Chim Acta 2:3314–3324CrossRefGoogle Scholar
  32. Sylla BS, Wild CP (2012) A million Africans a year dying from cancer by 2030: what can cancer research and control offer to the continent? Int J Cancer 130(2):245–250CrossRefPubMedGoogle Scholar
  33. Thati B, Noble A, Creaven BS, Walsh M, McCann M, Devereux M, Kavanagh K, Egan DA (2009) Role of cell cycle events and apoptosis in mediating the anti-cancer activity of a silver(I) complex of 4-hydroxy-3-nitro-coumarin-bis (phenanthroline) in human malignant cancer cells. Eur J Pharmacol 302:203–214CrossRefGoogle Scholar
  34. Vineis P, Wild CP (2014) Global cancer patterns: causes and prevention. Lancet 383(9916):549–557CrossRefPubMedGoogle Scholar
  35. Yilmaz VT, Gocmen E, Icsel C, Cengiz M, Susluer SY, Buyukgungor O (2014) Synthesis, crystal structures, in vitro DNA binding, antibacterial and cytotoxic activities of new di-and polynuclear silver(I) saccharinate complexes with tertiary monophosphanes. J Photochem Photobiol, B 131:31–42CrossRefGoogle Scholar
  36. Zimmermann KC, Bonzon CC, Green DR (2001) The machinery of programmed cell death. Pharmacol Ther 92:57–70CrossRefPubMedGoogle Scholar
  37. Zou H, Li Y, Liu X, Wang X (1999) An APAF-1· cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 274:11549–11556CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  1. 1.Department of BiochemistryUniversity of JohannesburgAuckland Park, JohannesburgSouth Africa
  2. 2.Department of Chemistry, Research Centre for Synthesis and CatalysisUniversity of JohannesburgAuckland Park, JohannesburgSouth Africa

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