Advertisement

A new triple system DNA-Nanosilver-Berberine for cancer therapy

  • Anna Grebinyk
  • Valeriy Yashchuk
  • Nataliya Bashmakova
  • Dmytro Gryn
  • Tobias Hagemann
  • Antonina Naumenko
  • Nataliya Kutsevol
  • Thomas Dandekar
  • Marcus Frohme
Original Article

Abstract

The isoquinoline quaternary alkaloid Berberine possesses a variety of pharmacological properties that suggests its promising application for an anticancer delivery system design utilizing its ability to intercalate DNA. In the current work, we have investigated the effects of Berberine on the human T cell leukemia cell line in vitro. Fluorescent microscopy of leukemic cells revealed Berberine nuclear localization. The results showed that Berberine inhibited leukemic cell growth in a time- and dose-dependent manner, that was associated with reactive oxygen species production intensification and caspase 3/7 activity increase with followed apoptosis induction. Berberine was used as a toxic and phototoxic agent for triple system synthesis along with DNA as a carrier and nanosilver as a plasmonic accelerator of Berberine electronic transitions and high energy emission absorbent centers. The proposed method allows to obtain the complex of DNA with Berberine molecules and silver nanoparticles. The optical properties of free components as well as their various combinations, including the final triple system DNA-Nanosilver-Berberine, were investigated. Obtained results support the possibility to use the triple system DNA-Nanosilver-Berberine as an alternative therapeutic agent for cancer treatment.

Keywords

Berberine Apoptosis Nanosilver DNA delivery system 

Notes

Acknowledgements

Authors are grateful to the German Academic Exchange Service for the support (scholarship 57129429, Anna Grebinyk).

Author contributions

The presented work was carried out in collaboration between all authors. YV, DT and FM coordinated the research work. GA estimated the leukemic cell viability, ROS production, Caspases 3/7 activity and Annexin staining, as well as performed the statistical analysis. HT performed fluorescent microscopy analysis. BN made spectral investigations of Berberine and Berberine-DNA system. GD performed spectral investigations of DNA-Nanosilver and DNA-Nanosilver-Berberine system. NA analyzed the spectral results. KN designed and synthesized the triple (DNA-Nanosilver-Berberine) system. GA and YV analyzed the data and wrote the manuscript. All authors discussed the results and commented on the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Open access

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

References

  1. Albring KF, Weidemüller J, Mittag S, Weiske J, Friedrich K, Geroni MC, Lombardi P, Huber O (2013) Berberine acts as a natural inhibitor of Wnt/β-catenin signaling—identification of more active 13-arylalkyl derivatives. Biofact 39(6):652–662.  https://doi.org/10.1002/biof.1133 CrossRefGoogle Scholar
  2. Andreazza LN, Vevert-Bizet C, Bourg-Heckly G, Sureau F, Salvador JM, Bonneau S (2016) Berberine as a photosensitizing agent for antitumoral photodynamic therapy: insights into its association to low density lipoproteins. Int J Pharm 510(1):240–249.  https://doi.org/10.1016/j.ijpharm.2016.06.009 CrossRefGoogle Scholar
  3. Arora A, Balasubramanian C, Kumar N, Agrawal S, Ojha RP, Maiti S (2008) Binding of Berberine to human telomeric quadruplex—spectroscopic, calorimetric and molecular modeling studies. FEBS J 275:3971–3983.  https://doi.org/10.1111/j.1742-4658.2008.06541.x CrossRefGoogle Scholar
  4. Basak D, Karan S, Mallik B (2006) Size selective photoluminescence in poly(methyl methacrylate) thin solid films with dispersed silver nanoparticles synthesized by a novel method. Chem Phys Lett 420:115–119.  https://doi.org/10.1016/j.cplett.2005.12.062 CrossRefGoogle Scholar
  5. Bazzicalupi C, Ferraroni M, Bilia AR, Scheggi F, Gratteri P (2013) The crystal structure of human telomeric DNA complexed with Berberine: an interesting case of stacked ligand to G-tetrad ratio higher than 1:1. Nucleic Acids Res 41:632–638.  https://doi.org/10.1093/nar/gks1001 CrossRefGoogle Scholar
  6. Cai Y, Xia Q, Luo R, Huang P, Sun Y, Shi Y, Jiang W (2014) Berberine inhibits the growth of human colorectal adenocarcinoma in vitro and in vivo. J Nat Med 68:53–62.  https://doi.org/10.1007/s11418-013-0766-z CrossRefGoogle Scholar
  7. Carmichael J, Degraff WG, Gazdar AF, Minna JD, Mitchell JB (1987) Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res 47:936–942. http://cancerres.aacrjournals.org/content/47/4/936.long
  8. Chalikian TV, Plum GE, Sarvazyan AP, Breslauer KJ (1994) Influence of drug binding on DNA hydration: acoustic and densimetric characterizations of netropsin binding to the poly(dAdT).poly(dAdT) and poly(dA).poly(dT) duplexes and the poly(dT).poly(dA).poly(dT) triplex at 25 degrees C. Biochem 33:8629–8640.  https://doi.org/10.1021/bi00195a003 CrossRefGoogle Scholar
  9. Cho Y, Lee JB, Hong J (2014) Controlled release of an anti-cancer drug from DNA structured nano-films. Sci Rep 4:4078.  https://doi.org/10.1038/srep04078 CrossRefGoogle Scholar
  10. Danilov VI, Dailidonis VV, Hovorun DM, Kurita N, Murayama Y, Natsume T, Potopalsky AI, Zaika LA (2006) Berberine alkaloid: quantum chemical study of different forms by the DFT and MP2 methods. Chem Phys Lett 430(4–6):409–413.  https://doi.org/10.1016/j.cplett.2006.09.026 CrossRefGoogle Scholar
  11. Dıez I, Kanyuk MI, Demchenko AP, Walther A, Jiang H, Robin OI, Ras HA (2012) Blue, green and red emissive silver nanoclusters formed in organic solvents. Nanoscale 4:4434.  https://doi.org/10.1039/C2NR30642E CrossRefGoogle Scholar
  12. Eruslanov E, Kusmartsev S (2010) Identification of ROS using oxidized DCFDA and flow-cytometry. Methods Mol Biol 594:57–72.  https://doi.org/10.1007/978-1-60761-411-1_4 CrossRefGoogle Scholar
  13. Fang Y, Seong NH, Dlott DD (2008) Measurement of the distribution of site enhancements in surface-enhanced Raman scattering. Science 321(5887):388–392.  https://doi.org/10.1126/science.1159499 CrossRefGoogle Scholar
  14. Florea AM, Büsselberg D (2011) Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers 3(1):1351–1371.  https://doi.org/10.3390/cancers3011351 CrossRefGoogle Scholar
  15. Franceschin M, Rossetti L, D’Ambrosio A, Schirripa S, Bianco A, Ortaggi G, Savino M, Schultes C, Neidle S (2006) Natural and synthetic G-quadruplex interactive Berberine derivatives. Bioorg Med Chem Lett 16(6):1707–1711.  https://doi.org/10.1016/j.bmcl.2005.12.001 CrossRefGoogle Scholar
  16. Gorrini Ch, Harris IS, Mak TW (2013) Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 12:931–947.  https://doi.org/10.1038/nrd4002 CrossRefGoogle Scholar
  17. Gumenyuk VG, Bashmakova NV, Kutovyy SYu, Yashchuk VM, Zaika LA (2012) Binding parameters of alkaloids Berberine and sanguinarine with DNA. Ukr J Phys 56(62011):524–533. https://arxiv.org/abs/1201.2579
  18. Hainfeld JF, Slatkin DN, Smilowitz HM (2004) The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol 49:309–315.  https://doi.org/10.1088/0031-9155/49/18/N03 CrossRefGoogle Scholar
  19. Hirakawa K, Hirano T (2008) The microenvironment of DNA switches the activity of singlet oxygen generation photosensitized by berberine and palmatine. Photochem Photobiol 84(1):202–208.  https://doi.org/10.1111/j.1751-1097.2007.00220.x Google Scholar
  20. Hirakawa K, Hirano T, Nishimura Y, Arai T, Nosaka Y (2012) Dynamics of singlet oxygen generation by DNA-binding photosensitizers. J Phys Chem B 116(9):3037–3044.  https://doi.org/10.1021/jp300142e CrossRefGoogle Scholar
  21. Jiang Q, Song C, Nangreave J, Liu X, Lin L, Qiu D, Wang ZG, Zou G, Liang X, Yan H, Ding B (2012) DNA origami as a carrier for circumvention of drug resistance. J Am Chem Soc 134(32):13396–13403.  https://doi.org/10.1021/ja304263n CrossRefGoogle Scholar
  22. Kang HC, Cho H, Bae YH (2015) DNA Polyplexes as combinatory drug carriers of doxorubicin and cisplatin: an in vitro study. Mol Pharm 12(8):2845–2857.  https://doi.org/10.1021/mp500873k CrossRefGoogle Scholar
  23. Kasyanenko N, Varshavskii M, Ikonnikov E, Tolstyko E, Belykh R, Sokolov P, Bakulev V, Rolich V, Lopatko K (2016) DNA modified with metal nanoparticles: preparation and characterization of ordered metal-DNA nanostructures in a solution and on a substrate. J Nanomat.  https://doi.org/10.1155/2016/3237250 Google Scholar
  24. Keasling J (2008) From yeast to alkaloids. Nat Chem Biol 4:524–525.  https://doi.org/10.1038/nchembio0908-524 CrossRefGoogle Scholar
  25. Li XL, Hu YJ, Wang H, Yu BQ, Yue HL (2012) Molecular spectroscopy evidence of Berberine binding to DNA: comparative binding and thermodynamic profile of intercalation. Biomacromol 13:873–880.  https://doi.org/10.1021/bm2017959 CrossRefGoogle Scholar
  26. Li J, Gu L, Zhang H, Liu T, Tian D, Zhou M, Zhou S (2013) Berberine represses DAXX gene transcription and induces cancer cell apoptosis. Lab Investig 93(3):354–364.  https://doi.org/10.1038/labinvest.2012.172 CrossRefGoogle Scholar
  27. Lin JP, Yang JS, Chang NW, Chiu TH, Su CC, Lu KW, Ho YT, Yeh CC, Mei-Dueyang, Lin HJ, Chung JG (2007) GADD153 mediates Berberine-induced apoptosis in human cervical cancer Ca Ski cells. Anticancer Res 27:3379–3386. https://ar.iiarjournals.org/content/27/5A/3379.long
  28. Linko V, Ora A, Kostiainen MA (2015) DNA nanostructures as smart drug-delivery vehicles and molecular devices. Trends Biotechnol 33(10):586–594.  https://doi.org/10.1016/j.tibtech.2015.08.001 CrossRefGoogle Scholar
  29. Kuo CL, Chi CW, Liu, TY (2005) Modulation of apoptosis by Berberine through inhibition of cyclooxygenase-2 and Mcl-1 expression in oral cancer cells. In Vivo 19(1):247–252. http://iv.iiarjournals.org/content/19/1/247.long
  30. Liu W, Zhang X, Liu P, Shen X, Lan T, Li W, Jiang Q, Xie X, Huang H (2010) Effects of Berberine on matrix accumulation and NF-kappa B signal pathway in alloxan-induced diabetic mice with renal injury. Eur J Pharmacol 638(1–3):150–155.  https://doi.org/10.1016/j.ejphar.2010.04.033 CrossRefGoogle Scholar
  31. Maiti M, Kumar GS (2007) Molecular aspects on the interaction of protoberberine, benzophenanthridine, and aristolochia group of alkaloids with nucleic acid structures and biological perspectives. Med Res Rev 27(5):649–695.  https://doi.org/10.1002/med.20087 CrossRefGoogle Scholar
  32. Mann J (2002) Natural products in cancer chemotherapy: past, present and future. Nat Rev Cancer 2:143–148.  https://doi.org/10.1038/nrc723 CrossRefGoogle Scholar
  33. Meeran SM, Katiyar S, Katiyar SK (2008) Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation. Toxicol Appl Pharmacol 229(1):33–43.  https://doi.org/10.1016/j.taap.2007.12.027 CrossRefGoogle Scholar
  34. Ming T, Chen H, Jiang R, Li Q, Wang J (2012) Plasmon-controlled fluorescence: beyond the intensity enhancement. J Phys Chem Lett 3(2):191–202.  https://doi.org/10.1021/jz201392k CrossRefGoogle Scholar
  35. Muskens OL, Giannini V, Sánchez-Gil JA, Rivas JG (2007) Strong enhancement of the radiative decay rate of emitters by single plasmonic nanoantennas. Nano Lett 7(9):2871–2875.  https://doi.org/10.1021/nl0715847 CrossRefGoogle Scholar
  36. Myhre O, Andersen JM, Aarnes H, Fonnum F (2003) Evaluation of the probes 20,70-dichlorofluorescin diacetate, luminol, and lucigenin as indicators of reactive species formation. Biochem Pharmacol 65:1575–1582.  https://doi.org/10.1016/S0006-2952(03)00083-2 CrossRefGoogle Scholar
  37. Neidle S (2017) Quadruplex nucleic acids as targets for anticancer therapeutics. Nat Rev Chem 1:0041.  https://doi.org/10.1038/s41570-017-0041 CrossRefGoogle Scholar
  38. Ortiz LMG, Lombardi P, Tillhon M, Scovassi AI (2014) Berberine, an epiphany against cancer. Mol 9:12349–12367.  https://doi.org/10.3390/molecules190812349 CrossRefGoogle Scholar
  39. Park SH, Sung JH, Kim EJ, Chung N (2015) Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines. Braz J Med Biol Res 48(2):111–119.  https://doi.org/10.1590/1414-431X20144293 CrossRefGoogle Scholar
  40. Patil JB, Kim J, Jayaprakasha GK (2010) Berberine induces apoptosis in breast cancer cells (MCF-7) through mitochondrial-dependent pathway. Eur J Pharmacol 645(1–3):70–78.  https://doi.org/10.1016/j.ejphar.2010.07.037 CrossRefGoogle Scholar
  41. Pereira GC, Branco AF, Matos JA, Pereira SL, Parke D, Perkins EL, Serafim TL, Sardão VA, Santos MS, Moreno AJ, Holy J, Oliveira PJ (2007) Mitochondrially Targeted Effects of Berberine (Natural Yellow 18, 5,6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo(5,6-a)quinolizinium) on K1735-M2 Mouse Melanoma Cells: comparison with Direct Effects on Isolated Mitochondrial Fractions. J Pharmacol Exper Ther 323(2):636–649.  https://doi.org/10.1124/jpet.107.128017 CrossRefGoogle Scholar
  42. Seo YS, Yim MJ, Kim BH, Kang KR, Lee SY, Oh JS, You JS, Kim SG, Yu SJ, Lee GJ, Kim DK, Kim CS, Kim JS, Kim JS (2015) Berberine-induced anticancer activities in FaDu head and neck squamous cell carcinoma cells. Oncol Rep 34:3025–3034.  https://doi.org/10.3892/or.2015.4312 CrossRefGoogle Scholar
  43. Serafim TL, Oliveira PJ, Sardao VA, Perkins E, Parke D, Holy J (2008) Different concentrations of Berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line. Cancer Chemother Pharmacol 61:1007–1018.  https://doi.org/10.1007/s00280-007-0558-9 CrossRefGoogle Scholar
  44. Suzuki J, Denning DP, Imanishi EH, Horvitz R, Nagata Sh (2013) Xk-Related protein 8 and CED-8 promote phosphatidylserine exposure in apoptotic cells. Science 341(6144):403–406.  https://doi.org/10.1126/science.1236758 CrossRefGoogle Scholar
  45. Tacar O, Sriamornsak P, Dass CR (2013) Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 65(2):157–170.  https://doi.org/10.1111/j.2042-7158.2012.01567.x CrossRefGoogle Scholar
  46. Wang Y, Kheir MM, Chai Y, Hu J, Xing D, Lei F, Du L (2011) Comprehensive study in the inhibitory effect of Berberine on gene transcription, including TATA box. PLoS One 6:e23495.  https://doi.org/10.1371/journal.pone.0023495 CrossRefGoogle Scholar
  47. Wang N, Zhu M, Wang X, Tan HY, Tsao SW, Feng Y (2014) Berberine-induced tumor suppressor p53 up-regulation gets involved in the regulatory network of MIR-23a in hepatocellular carcinoma. Biochimica Biophys Acta 9:849–857.  https://doi.org/10.1016/j.bbagrm.2014.05.027 CrossRefGoogle Scholar
  48. Wu HL, Hsu CY, Liu WH, Yung BY (1999) Berberine-induced apoptosis of human leukemia HL-60 cells is associated with down-regulation of nucleophosmin/B23 and telomerase activity. Int J Cancer. 81(6):923–929. https://doi.org/10.1002/(SICI)1097-0215(19990611)81:6<923::AID-IJC14>3.0.CO;2-DGoogle Scholar
  49. Xiao N, Chen S, Ma Y, Qiu J, Tan JH, Ou TM, Gu LQ, Huang ZS, Li D (2012) Interaction of Berberine derivative with protein POT1 affect telomere function in cancer cells. Biochem Biophys Res Commun 419:567–572.  https://doi.org/10.1016/j.bbrc.2012.02.063 CrossRefGoogle Scholar
  50. Xu H, Suslick KS (2010) Water-soluble fluorescent silver nanoclusters. Adv Mater 22:1078–1082.  https://doi.org/10.1002/adma.200904199 CrossRefGoogle Scholar
  51. Yashchuk VM, Kudrya VYu (2017) The spectral properties of DNA and RNA macromolecules at low temperatures: fundamental and applied aspects. Method Appl Fluoresc 5:014001.  https://doi.org/10.1088/2050-6120/aa50c9 CrossRefGoogle Scholar
  52. Yashchuk VM, Kudrya VYu, Losytskyy MYu, Dubey IYA, Suga H (2007) Electronic excitation energy transfer in DNA. Nature of triplet excitations capturing centers. Mol Cryst Liq Cryst 467:311–323.  https://doi.org/10.1080/15421400701224751 CrossRefGoogle Scholar
  53. Yeshchenko OA, Dmitruk IM, Alexeenko AA, Losytskyy MY, Kotko AV, Pinchuk AO (2009) Size-dependent surface-plasmon-enhanced photoluminescence from silver nanoparticles embedded in silica. Phys Rev B 79:235438.  https://doi.org/10.1103/PhysRevB.79.235438 CrossRefGoogle Scholar
  54. Zhang W, Tung CH (2017) Sequence-independent DNA nanogel as a potential drug carrier. Macromol Rapid Commun 8(20):1700366.  https://doi.org/10.1002/marc.201700366 CrossRefGoogle Scholar
  55. Zhang A, Zhanga J, Fang Y (2008) Photoluminescence from colloidal silver nanoparticles. J Lumin 128(10):1635–1640.  https://doi.org/10.1016/j.jlumin.2008.03.014 CrossRefGoogle Scholar
  56. Zhang X, Gu L, Li J, Shah N, He J, Yang L, Hu Q, Zhou M (2010) Degradation of MDM2 by the interaction between Berberine and DAXX leads to potent apoptosis in MDM2-overexpressing cancer cells. Cancer Res 70(23):9895–9904.  https://doi.org/10.1158/0008-5472.CAN-10-1546 CrossRefGoogle Scholar
  57. Zhang J, Cao H, Zhang B, Cao H, XuX Ruan H, Yi T, Tan L, Qu R, Song G, Wang B, Hu T (2013) Berberine potently attenuates intestinal polyps growth in ApcMin mice and familial adenomatous polyposis patients through inhibition of Wnt signalling. J Cell Mol Med 17(11):484–1493.  https://doi.org/10.1111/jcmm.12119 CrossRefGoogle Scholar
  58. Zheng Y, Hunting DJ, Ayotte P, Sanche L (2008) Radiosensitization of DNA by gold nanoparticles irradiated with high-energy electrons. Radiat Res 169:19–27.  https://doi.org/10.1667/RR1080.1 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Technical University of Applied Sciences WildauWildauGermany
  2. 2.Taras Shevchenko National University of KyivKievUkraine
  3. 3.BiocenterUniversity of WürzburgWürzburgGermany

Personalised recommendations