Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers

Kreft D, Wang Y, Rattay M, Tönsing K, Anselmetti D (2018)
Journal of Nanobiotechnology 16(1): 56.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
Download
OA 1.18 MB
Abstract / Bemerkung
Background Chemotherapeutic agents (anti-cancer drugs) are small cytostatic or cytotoxic molecules that often bind to double-stranded DNA (dsDNA) resulting in modifications of their structural and nanomechanical properties and thus interfering with the cell proliferation process. Methods We investigated the anthraquinone compound mitoxantrone that is used for treating certain cancer types like leukemia and lymphoma with magnetic tweezers as a single molecule nanosensor. In order to study the association of mitoxantrone with dsDNA, we conducted force-extension and mechanical overwinding experiments with a sensitivity of 10−14 N. Results Using this method, we were able to estimate an equilibrium constant of association Ka ≈ 1 × 105 M−1 as well as a binding site size of n ≈ 2.5 base pairs for mitoxantrone. An unwinding angle of mitoxantrone-intercalation of ϑ ≈ 16° was determined. Conclusion Moreover, we observed a complex concentration-dependent bimodal binding behavior, where mitoxantrone associates to dsDNA as an intercalator and groove binder simultaneously at low concentrations and as a mere intercalator at high concentrations.
Stichworte
Mitoxantrone DNA Magnetic tweezers Intercalator Groove binder
Erscheinungsjahr
2018
Zeitschriftentitel
Journal of Nanobiotechnology
Band
16
Ausgabe
1
Art.-Nr.
56
ISSN
1477-3155
eISSN
1477-3155
Page URI
https://pub.uni-bielefeld.de/record/2930250

Zitieren

Kreft D, Wang Y, Rattay M, Tönsing K, Anselmetti D. Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers. Journal of Nanobiotechnology. 2018;16(1): 56.
Kreft, D., Wang, Y., Rattay, M., Tönsing, K., & Anselmetti, D. (2018). Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers. Journal of Nanobiotechnology, 16(1), 56. doi:10.1186/s12951-018-0381-y
Kreft, D., Wang, Y., Rattay, M., Tönsing, K., and Anselmetti, D. (2018). Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers. Journal of Nanobiotechnology 16:56.
Kreft, D., et al., 2018. Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers. Journal of Nanobiotechnology, 16(1): 56.
D. Kreft, et al., “Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers”, Journal of Nanobiotechnology, vol. 16, 2018, : 56.
Kreft, D., Wang, Y., Rattay, M., Tönsing, K., Anselmetti, D.: Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers. Journal of Nanobiotechnology. 16, : 56 (2018).
Kreft, Dennis, Wang, Ying, Rattay, Michael, Tönsing, Katja, and Anselmetti, Dario. “Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers”. Journal of Nanobiotechnology 16.1 (2018): 56.
Alle Dateien verfügbar unter der/den folgenden Lizenz(en):
Copyright Statement:
This Item is protected by copyright and/or related rights. [...]
Volltext(e)
Access Level
OA Open Access
Zuletzt Hochgeladen
2019-09-06T09:19:00Z
MD5 Prüfsumme
6d3af2268e0d46a8c146e08fb95aec0f

1 Zitation in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

Correction to: Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers.
Kreft D, Wang Y, Rattay M, Toensing K, Anselmetti D., J Nanobiotechnology 17(1), 2019
PMID: 30736797

63 References

Daten bereitgestellt von Europe PubMed Central.


AUTHOR UNKNOWN, 0
Antitumor agents. 1. 1,4-Bis[(aminoalkyl)amino]-9,10-anthracenediones.
Murdock KC, Child RG, Fabio PF, Angier RB, Wallace RE, Durr FE, Citarella RV., J. Med. Chem. 22(9), 1979
PMID: 490545
On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs.
Wu CC, Li YC, Wang YR, Li TK, Chan NL., Nucleic Acids Res. 41(22), 2013
PMID: 24038465
Mitoxantrone, cyclophosphamide, and 5-fluorouracil in the treatment of hormonally unresponsive metastatic breast cancer.
Holmes FA, Yap HY, Esparza L, Buzdar AU, Hortobagyi GN, Blumenschein GR., Semin. Oncol. 11(3 Suppl 1), 1984
PMID: 6385262
Mitoxantrone in the treatment of acute myelogenous leukemia: a review.
Thomas X, Archimbaud E., Hematol Cell Ther 39(4), 1997
PMID: 9352324
Mitoxantrone: a review of its use in multiple sclerosis.
Scott LJ, Figgitt DP., CNS Drugs 18(6), 2004
PMID: 15089110
Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial.
Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, Ancliff P, Morgan M, Masurekar A, Goulden N, Green N, Revesz T, Darbyshire P, Love S, Saha V., Lancet 376(9757), 2010
PMID: 21131038
Mitoxantrone: an overview of safety and toxicity.
Posner LE, Dukart G, Goldberg J, Bernstein T, Cartwright K., Invest New Drugs 3(2), 1985
PMID: 3894276
Development of mitoxantrone.
White RJ, Durr FE., Invest New Drugs 3(2), 1985
PMID: 2410393
The effect of doxorubicin and its analogue mitoxantrone on cardiac muscle and on serum lipids: an experimental study.
Koutinos G, Stathopoulos GP, Dontas I, Perrea-Kotsarelis D, Couris E, Karayannacos PE, Deliconstantinos G., Anticancer Res. 22(2A), 2002
PMID: 12014656
A molecular understanding of mitoxantrone-DNA adduct formation: effect of cytosine methylation and flanking sequences.
Parker BS, Buley T, Evison BJ, Cutts SM, Neumann GM, Iskander MN, Phillips DR., J. Biol. Chem. 279(18), 2004
PMID: 14963025
Mitoxantrone: an agent with promises for anticancer therapies
Varadwaj P, Misra K, Sharma A, Kumar R., 2010
Interactions of antitumor agents Ametantrone and Mitoxantrone (Novatrone) with double-stranded DNA.
Kapuscinski J, Darzynkiewicz Z., Biochem. Pharmacol. 34(24), 1985
PMID: 4074383
Aminoacyl-analogues of mitoxantrone as novel DNA-damaging cytotoxic agents
Zagotto G, Sissi C, Palumbo G., 2004
Intercalative interaction of the anticancer drug mitoxantrone with double stranded DNA: a calorimetric characterization of the energetics
Bhattacharyya J, Basu A, Suresh Kumar., 2014
The elasticity of a single supercoiled DNA molecule.
Strick TR, Allemand JF, Bensimon D, Bensimon A, Croquette V., Science 271(5257), 1996
PMID: 8596951
Behavior of supercoiled DNA.
Strick TR, Allemand JF, Bensimon D, Croquette V., Biophys. J. 74(4), 1998
PMID: 9545060
Magnetic tweezers for single-molecule experiments
Vilfan ID, Lipfert J, Koster DA, Lemay SG, Dekker NH., 2009
Rational design of a cytotoxic dinuclear Cu2 complex that binds by molecular recognition at two neighboring phosphates of the DNA backbone.
Jany T, Moreth A, Gruschka C, Sischka A, Spiering A, Dieding M, Wang Y, Samo SH, Stammler A, Bogge H, Fischer von Mollard G, Anselmetti D, Glaser T., Inorg Chem 54(6), 2015
PMID: 25650993
Rational design of dinuclear complexes binding at two neighboring phosphate esters of DNA
Glaser T, von GF, Anselmetti D., 2016
Binding mechanism of PicoGreen to DNA characterized by magnetic tweezers and fluorescence spectroscopy.
Wang Y, Schellenberg H, Walhorn V, Toensing K, Anselmetti D., Eur. Biophys. J. 46(6), 2017
PMID: 28251265

AUTHOR UNKNOWN, 0
Nanomechanics of Fluorescent DNA Dyes on DNA Investigated by Magnetic Tweezers.
Wang Y, Sischka A, Walhorn V, Tonsing K, Anselmetti D., Biophys. J. 111(8), 2016
PMID: 27760348
Entropic elasticity of lambda-phage DNA.
Bustamante C, Marko JF, Siggia ED, Smith S., Science 265(5178), 1994
PMID: 8079175
Estimating the persistence length of a worm-like chain molecule from force-extension measurements.
Bouchiat C, Wang MD, Allemand J, Strick T, Block SM, Croquette V., Biophys. J. 76(1 Pt 1), 1999
PMID: 9876152
Quantifying force-dependent and zero-force DNA intercalation by single-molecule stretching.
Vladescu ID, McCauley MJ, Nunez ME, Rouzina I, Williams MC., Nat. Methods 4(6), 2007
PMID: 17468764
Binding kinetics of bisintercalator Triostin a with optical tweezers force mechanics.
Kleimann C, Sischka A, Spiering A, Tonsing K, Sewald N, Diederichsen U, Anselmetti D., Biophys. J. 97(10), 2009
PMID: 19917232
Study on the interaction of anticancer drug mitoxantrone with DNA by fluorescence and Raman spectroscopies
Tang L., 2006
Calculation of binding isotherms for heterogenous polymers.
Crothers DM., Biopolymers 6(4), 1968
PMID: 5644787
Studies of the binding of actinomycin and related compounds to DNA.
Muller W, Crothers DM., J. Mol. Biol. 35(2), 1968
PMID: 4107107
DNA intercalation: helix unwinding and neighbor-exclusion
Williams LD, Eglifgb M, Gao Q, Ricfgh A., 1992
Stretching of macromolecules and proteins
Strick TR, Dessinges M-N, Charvin G, Dekker NH, Allemand J-F, Bensimon D., 2003
Magnetic tweezers measurements of the nanomechanical properties of DNA in the presence of drugs.
Salerno D, Brogioli D, Cassina V, Turchi D, Beretta GL, Seruggia D, Ziano R, Zunino F, Mantegazza F., Nucleic Acids Res. 38(20), 2010
PMID: 20601682

Rutkauskas M, Krivoy A, Szczelkun MD, Rouillon C, Seidel R., 2017
Biophysical characterization of the association of histones with single-stranded DNA.
Wang Y, van Merwyk L, Tonsing K, Walhorn V, Anselmetti D, Fernandez-Busquets X., Biochim Biophys Acta Gen Subj 1861(11 Pt A), 2017
PMID: 28756274
Mechanical and structural properties of YOYO-1 complexed DNA.
Gunther K, Mertig M, Seidel R., Nucleic Acids Res. 38(19), 2010
PMID: 20511588
Torsional sensing of small-molecule binding using magnetic tweezers.
Lipfert J, Klijnhout S, Dekker NH., Nucleic Acids Res. 38(20), 2010
PMID: 20624816
Direct observation of R-loop formation by single RNA-guided Cas9 and Cascade effector complexes.
Szczelkun MD, Tikhomirova MS, Sinkunas T, Gasiunas G, Karvelis T, Pschera P, Siksnys V, Seidel R., Proc. Natl. Acad. Sci. U.S.A. 111(27), 2014
PMID: 24912165
Directional R-Loop Formation by the CRISPR-Cas Surveillance Complex Cascade Provides Efficient Off-Target Site Rejection.
Rutkauskas M, Sinkunas T, Songailiene I, Tikhomirova MS, Siksnys V, Seidel R., Cell Rep 10(9), 2015
PMID: 25753419
Interaction of oxazole yellow dyes with DNA studied with hybrid optical tweezers and fluorescence microscopy.
Murade CU, Subramaniam V, Otto C, Bennink ML., Biophys. J. 97(3), 2009
PMID: 19651041
Strong DNA deformation required for extremely slow DNA threading intercalation by a binuclear ruthenium complex.
Almaqwashi AA, Paramanathan T, Lincoln P, Rouzina I, Westerlund F, Williams MC., Nucleic Acids Res. 42(18), 2014
PMID: 25245944
The impact of DNA intercalators on DNA and DNA-processing enzymes elucidated through force-dependent binding kinetics.
Biebricher AS, Heller I, Roijmans RF, Hoekstra TP, Peterman EJ, Wuite GJ., Nat Commun 6(), 2015
PMID: 26084388
Mechanisms of small molecule-DNA interactions probed by single-molecule force spectroscopy.
Almaqwashi AA, Paramanathan T, Rouzina I, Williams MC., Nucleic Acids Res. 44(9), 2016
PMID: 27085806
Acridine orange association equilibrium in aqueous solution
Costantino L, Guarino G, Ortona O, Vitagllano V., 1984
Binding affinity and site selectivity of daunomycin analogues.
Roche CJ, Berkowitz D, Sulikowski GA, Danishefsky SJ, Crothers DM., Biochemistry 33(4), 1994
PMID: 8305441
Binding of a homologous series of anthraquinones to DNA.
McKnight RE, Zhang J, Dixon DW., Bioorg. Med. Chem. Lett. 14(2), 2004
PMID: 14698168
Binding mechanism of fluorescent dyes to DNA characterized by magnetic tweezers
Wang Y, Schellenberg H, Walhorn V, Toensing K, Anselmetti D., 2017

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 30005668
PubMed | Europe PMC

Suchen in

Google Scholar