Abstract
Two new ruthenium (II) polypyridyl complexes [Ru(MeIm)4(pip)]2+ (1) and [Ru(MeIm)4(4-npip)]2+ (2) were synthesized under the guidance of computational studies (DFT). Their binding property to human telomeric G-quadruplex studied by UV–Vis absorption spectroscopy, the fluorescent resonance energy transfer (FRET) melting assay and circular dichroism (CD) spectroscopy for validating the theoretical prediction. Both of them were evaluated for their potential anti-proliferative activity against four human tumor cell lines. Complex 2 shows growth inhibition against all the cell lines tested, especially the human lung tumor cell (A549). The RTCA analysis not only validated the inhibition activity but also showed the ability of reducing A549 cells’ migration. DNA-flow cytometric analysis, mitochondrial membrane potential (ΔΨm) and the scavenger measurements of reactive oxygen species (ROS) analysis carried out to investigate the mechanism of cell growth inhibition and apoptosis-inducing effect of complex 2. The results demonstrated that complex 2 induces tumor cells apoptosis by acting on both mitochondrial homeostasis destruction and death receptor signaling pathways. And those suggested that complex 2 could be a candidate for further evaluation as a chemotherapeutic agent against human tumor.
Similar content being viewed by others
References
Jamieson ER, Lippard SJ (1999) Chem Rev 99:2467–2498
Albers J, Chaudhry V, Donehower R, Cavaletti G (2014) Cochrane Database Syst Rev 3:CD005228
Galanski M, Arion VB, Jakupec MA, Keppler BK (2003) Curr Pharm Des 9:2078–2089
Garber SB, Kingsbury JS, Gray BL, Hoveyda AH (2001) J Am Chem Soc 123:3186
Kingsbury JS, Harrity JPA, Bonitatebus PJ, Hoveyda AH (1999) J Am Chem Soc 121:791–799
Srishailam A, Kumar YP, Reddy PV, Nambigari N, Vuruputuri U, Singh SS, Satyanarayana S (2014) J Photochem Photobiol B 132:111–123
Zhenqiang W, Cohen SM (2011) Dissertations & Theses—Gradworks 38:1315–29
Farha OK, Hupp JT (2010) Acc Chem Res 43:1166–1175
Fyfe MCT, Stoddart JF (1997) Acc Chem Res 30:393–401
Norbert S, Shyam B (2011) Chem Rev 112:933–969
Ryan P, Farha OK, Broadbelt LJ, Snurr RQ (2011) AIChE J 57:1759–1766
Leininger S, Olenyuk B, Stang PJ (2000) Chem Rev 100:853–908
José C, Conor B, Jorunn S (2003) Juan Modesto CJ, Francesc L, Miguel. J Inorg Chem 42:8716–8727
Mishra S, Pfalzgraf LG, Jeanneaub E, Chermettec H (2007) Dalton Trans 4:410–413
Tangoulis V, Raptopoulou CP, Terzis A, Paschalidou S, Perlepes SP, Bakalbassis EG (1997) Inorg Chem 36:3996–4006
Edfors O, Sandell M, Beek JJVD, Wilson SK, Börjesson PO (2000) Wireless Pers Commun 12:55–70
García G, Atilhan M, Aparicio S (2015) Theor Chem Acc 134:1–13
Wiberg KB, Stratmann RE, Frisch MJ (1998) Chem Phys Lett 297:60–64
Liu D, Liu Y, Wang C, Shi S, Sun D, Gao F, Zhang Q, Liu J (2012) Chem Plus Chem 77:551–562
Mceachern MJ, Krauskopf A, Blackburn EH (2000) Annu Rev Genet 34:331–358
Yang X, Chen L, Liu Y, Yang Y, Chen T, Zheng W, Liu J, He Q-Y (2012) Biochimie 94:345–353
Chen LM, Liu J, Chen JC, Tan CP, Shi S, Zheng KC, Ji LN (2008) J Inorg Biochem 102:330–341
Liu J, Zheng W, Shi S, Tan C, Chen J, Zheng K, Ji L (2008) J Inorg Biochem 102:193–202
Sun DD, Liu Y, Liu D, Zhang R, Yang X, Liu J (2012) Chem Eur J 18:4285–4295
Sun DD, Wang WZ, Mao JW, Mei WJ, Liu J (2012) Bioorg Med Chem Lett 22:102–105
Sun DD, Zhang R, Yuan F, Liu D, Zhou Y, Liu J (2012) Dalton Trans 41:1734–1741
Avakyan VG, Gromak VV (2001) J Appl Spectrosc 68:401–409
Yang W, Parr RG (1985) Proc Natl Acad Sci 82:6723–6726
Becke AD (1993) J Chem Phys 98:1372–1377
Becke AD (1993) J Chem Phys 98:5648–5652
Lee C, Yang W, Parr RG (1988) Phys Rev B 37:785
Hay PJ, Wadt WR (1985) J Chem Phys 82:270–283
Juris A, Balzani V, Barigelletti F, Campagna S, Belser PL, Von Zelewsky A (1988) Coordin Chem Rev 84:85–277
Car R, Parrinello M (1985) Phys Rev Lett 55:2471–2474
Barone V, Cossi M (1998) J Phys Chem A 102:1995–2001
Cossi M, Rega N, Scalmani G, Barone V (2003) J Comput Chem 24:669–681
Schaftenaar G, Noordik JH (2000) Molden. J Comput Aid Mol Des 14:123–134
Fantacci S, Angelis FD, Sgamellotti A, Marrone A, Re N (2005) J Am Chem Soc 127:14144–14145
Cantor CR, Warshaw MM, Shapiro H (1970) Biopolymers 9:1059–1077
Marmur J, Doty P (1961) J Mol Biol 3:585–594
Krupp G, Kuhne K, Tamm S, Klapper W, Heidorn K, Rott A, Parwaresch R (1997) Nucleic Acids Res 25:919–921
Kim NW, Wu F (1997) Nucleic Acids Res 25:2595–2597
Reed JE, Arnol AA, Neidle S, Vilar R (2006) J Am Chem Soc 128:5992–5993
Whiteman M, Dogra Y, Winyard PG, Armstrong JS (2009) Methods. Mol Biol 476:28–49
Myhre O, Andersen JM, Aarnes H, Fonnum F (2003) Biochem Pharmacol 10:1572–1582
Carter MT, Rodriguez M, Bard AJ (1989) J Am Chem Soc 111:8901–8911
Nair RB, Teng ES, Kirkland SL, Murphy CJ (1998) Inorg Chem 37:139–141
Neyhart GA, Grover N, Smith SR, Kalsbeck WA, Fairley TA, Cory M, Thorp HH (1993) J Am Chem Soc 115:4423–4428
Clegg RM, Murchie AI, Zechel A, Carlberg C, Diekmann S, Lilley DM (1992) Biochemistry 31:4846–4856
Meade TJ, Kayyem JF (1995) Chem Int Ed 34:352–354
Sogami M, Era S, Nagaoka S, Inouye H (1982) Int J Pept Protein Res 19:263–269
Debnath D, Kumar GS, Maiti M (1991) J Biomol Struct Dyn 9:61–79
Bergamo A, Sava G (2007) Dalton Trans 251:1267–1272
Choi LMR, Kim NW, Zuo JJ, Robert Gerbing MA, Dan S, Lukens JN, Matthay KK, Seeger RC, Reynolds CP (2000) Med Pediatr Oncol 35:647–650
Kroemer G, Reed JC (2000) Nat Med 6:513–519
Pelicano H, Carney D, Peng H (2004) Drug Resist Update 7:97–110
Turrens JF (2003) J Physiol London 552:335–344
Acknowledgments
We would like to thank our co-workers of the biotechnology center of Anhui Agriculture University for their technical supports. This work was supported by the National Natural Science Foundation of China (21401002), the Natural Science Foundation of Anhui Province, China (1508085QB37), the Youth Science Fund Key Project of Anhui Agricultural University (2013ZR011). This research leading to these results has also received funding from the Science Foundation of Young Teachers of Anhui Agricultural University (ZHSJ2013057), and the New Specialty of Biopharmaceutical Construction of Anhui Agricultural University (SJJD201313).
Author information
Authors and Affiliations
Corresponding author
Additional information
D. Sun and Z. Mou contribute equally to this work.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Sun, D., Mou, Z., Li, N. et al. Anti-tumor activity and mechanism of apoptosis of A549 induced by ruthenium complex. J Biol Inorg Chem 21, 945–956 (2016). https://doi.org/10.1007/s00775-016-1391-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00775-016-1391-6