A new triple system DNA-Nanosilver-Berberine for cancer therapy
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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.
KeywordsBerberine Apoptosis Nanosilver DNA delivery system
Authors are grateful to the German Academic Exchange Service for the support (scholarship 57129429, Anna Grebinyk).
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.
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- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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