Normal human genomic DNA (N-DNA) and mutated DNA (M-DNA) from K562 leukemic cells show different thermodynamic properties and binding affinities on interaction with anticancer drugs; adriamycin (ADR) and daunomycin (DNM). Isothermal calorimetric thermograms representing titration of ADR/DNM with N-DNA and M-DNA on analysis best fitted with sequential model of four and three events respectively. From Raman spectroscopy it has been identified that M-DNA is partially transformed to A form owing to mutations and N-DNA on binding of drugs too undergoes transition to A form of DNA. A correlation of thermodynamic contribution and structural data reveal the presence of different binding events in drug and DNA interactions. These events are assumed to be representative of minor groove complexation, reorientation of the drug in the complex, DNA deformation to accommodate the drugs and finally intercalation. Dynamic light scattering and zeta potential data also support differences in structure and mode of binding of N and M DNA. This study highlights that mutations can manifest structural changes in DNA, which may influence the binding efficacy of the drugs. New generation of drugs can be designed which recognize the difference in DNA structure in the cancerous cells instead of their biochemical manifestation.
References
[1]
Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, et al. (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Eng J Med 355: 2408–2417.
[2]
Comogilo PM, Giordano S, Trusolino L (2008) Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nature Rev Drug Discov 7: 504–516.
[3]
Couzin J (2002) Cancer drugs. Smart weapons prove tough to design. Science 298: 522–525.
[4]
Frantz S (2005) Drug discovery: playing dirty. Nature 437: 942–943.
[5]
Frantz S (2006) Drug approval triggers debate on future direction for cancer treatments. Nature Rev Drug Discov 5: 91.
[6]
Ghosh D, Saha C, Hossain M, Dey SK, Kumar GS (2013) Biophysical studies of mutated K562 DNA (erythroleukemic cells) binding to adriamycin and daunomycin reveal that mutations induce structural changes influencing binding behavior. J Biomol Struct Dyn 31: 331–341.
[7]
Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L (2004) Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 56: 185–229.
[8]
Tewey KM, Rowe TC, Yang L, Halligan BD, Liu LF (1984) Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science 2v26, 466–468.
[9]
Sordet O, Khan QA, Kohn KW, Pommier Y (2003) Apoptosis induced by topoisomerase inhibitors. Curr Med Chem Anti-cancer Agents 3: 271–290.
[10]
Chaires JB, Herrera JE, Waring MJ (1990) Preferential binding of daunomycin to 5′ATCG and 5′ATGC sequences revealed by footprinting titration experiments. Biochemistry 29: 6145–6153.
[11]
Chaires JB, Fox KR, Herrera JE, Britt M, Waring MJ (1987) Site and sequence specificity of the daunomycin-DNA interaction. Biochemistry 26: 8227–8236.
[12]
Skorobogaty A, White RJ, Phillips DR, Reiss JA (1988) The 5′-CA DNA-sequence preference of daunomycin. FEBS Letters 227: 103–106.
[13]
Quigley GJ, Wang AHJ, Ughetto G, Marel GV, Boom JHV, et al. (1980) Molecular structure of an anticancer drug-DNA complex: Daunomycin plus d(CpGpTpApCpG). Proc Natl Acad Sci USA 77: 7204–7208.
[14]
Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, et al. (2008) DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 456: 66–72.
[15]
Ghosh D, Hossain M, Saha C, Dey SK, Kumar GS (2012) Intercalation and induction of strand breaks by adriamycin and daunomycin: a study with human genomic DNA. DNA Cell Biol 31: 378–387.
[16]
Rameta DP, Mudd CP, Berger RL, Breslauer KJ (1993) Thermodynamic characterization of daunomycin-DNA interactions: comparison of complete binding profiles for a series of DNA host duplexes. Biochemistry 32: 5064.
Krisnamoorthy CR, Yen SF, Smith JC, Lown JW, Wilson WD (1986) Stopped- flow kinetic analysis of the interaction of anthraquinone anticancer drugs with calf thymus DNA, poly[d(G-C)].poly[d(G-C)], and poly[d(A-T)].poly[d(A-T)]. Biochemistry 25: 5933.
[19]
Qu X, Wan C, Becker HC, Zhoung D, Zewail AH (2001) The anticancer drug-DNA complex: femtosecond primary dynamics for anthracycline antibiotics function. Proc. Natl Acad Sci USA 98: 14212.
[20]
Chaires JB, Dattagupta N, Crothers DM (1985) Kinetics of the daunomycin-DNA interaction. Biochemistry 24: 260.
[21]
Wilhelm M, Mukherjee A, Bouvier B, Zakrzewska K, Hynes JT, et al. (2012) Multistep drug intercalation: molecular dynamics and free energy studies of the binding of daunomycin to DNA. J Am Chem Soc 134: 8588–8596.
[22]
Rizzo V, Sacchi N, Menozzi M (1989) Kinetic studies of anthracycline-DNA interaction by fluorescence stopped flow confirm a complex association mechanism. Biochemistry 28: 274.
[23]
Neault JF, Naoui M, Tajmir-Riahi HA (1989) DNA-drug interaction. The effects of vitamin C on the solution structure of Calf-thymus DNA studied by FTIR and laser Raman difference spectroscopy. J Biomol Struct Dyn 13: 387–397.
[24]
Benevides JM, Thomas GJ (1983) Characterization of DNA structures by Raman spectroscopy: high-salt and low-salt forms of double helical poly(dG-dC) in H2O and D2O solutions and application to B, Z and A-DNA. Nucleic Acids Res 11: 5747.
[25]
Wartell RM, Klysik J, Hillen W, Wells RD (1982) Junction between Z and B conformation in a DNA restriction fragment: Evaluation by Raman Spectroscopy. Proc Natl Acad Sci USA 79: 2549–2553.
[26]
Ding Y, Zhang L, Xie J, Guo R (2010) Binding characteristics and molecular mechanism of interaction between ionic liquid and DNA. J Phys Chem B 114: 2033–2043.
[27]
Majumder P, Dasgupta D (2011) Effect of DNA groove binder distamycin A upon chromatin structure. PlosOne 6: e26486 doi:10.1371/journal.pone.0026486.
[28]
Salvia MV, Addison F, Alniss HY, Buurma NJ, Khalaf AI, et al. (2013) Thiazotropsin aggregation and its relationship to molecular recognition in the DNA minor groove. Biophys Chem 179: 1–11.
[29]
Chaires JB, Satyanarayana S, Suh D, Fokt I, Przewloka T, et al. (1996) Parsing the free energy of anthracycline antibiotic binding to DNA. Biochemistry 35: 2047.
[30]
Arora A, Maiti S (2008) Effect of Loop Orientation on Quadruplex-TMPyP4 Interaction. J Phys Chem B 112: 8151–8159.
[31]
Benevides JM, Overman SA, Thomas GJ Jr (2005) Raman, polarized Raman and ultraviolet resonance Raman spectroscopy of nucleic acids and their complexes. J Raman Spectrosc 36: 279–299.
[32]
Neault JF, Tajmir-Riahi HA (1996) Diethylstilbestrol-DNA interaction studied by Fourier transform infrared and Raman spectroscopy. J Biol Chem 271: 8140–8143.
[33]
Yoshikawa Y, Yoshikawa K, Kanbe T (1996) Daunomycin unfolds compactly packed DNA. Biophys Chem 61: 93–100.
[34]
He Y, Shang Y, Liu Z, Shao S, Liu H, et al.. (2013) Interactions between ionic liquid surfactant [C12mim]Br and DNA in dilute brine. Colloids Surf B Biointerfaces 101: : 398–404.
[35]
Nishimura Y, Tsuboi M, Nakano T, Higuchi S, Sato T, et al. (1983) Raman diagnosis of nucleic acid structure: sugar-puckering and glycosidic conformation in the guanosine moiety. Nucleic Acid Res 11: 1579–1588.
[36]
Serban D, Benevides JM, Thomas GJ (2002) DNA secondary structure and Raman markers of supercoiling in Escherichia coli plasmid pUC19. Biochemistry 41: , 847.
[37]
Dong J, Drohat AC, Stivers JT, Pankiewicz KW, Carey PR (2000) Raman spectroscopy of uracil DNA glycosylase-DNA complexes: insights into DNA damage recognition and catalysis. Biochemistry 39: 13241.
[38]
Li G, Yang H, Xu Y, Zhang Z (2002) Raman microspectroscopic study of biomolecular structure inside living adhesive cells. Sci China C Life Sci 45: 397.
[39]
Movileanu L, Benevides JM, Thomas GJ (1999) Temperature dependence of the raman spectrum of DNA. Part I-Raman signatures of premelting and melting transitions of poly (dA–dT)· poly (dA–dT). J. Raman Spectrosc 30: 637.
[40]
Ling JY, Yang QZ, Luo SS, Li Y, Zhang CK (2005) Preliminary study on cordycepin-DNA interaction by Raman spectroscopy. Chinese Chem Lett 16: 71–74.
[41]
Mady MM, Ghannam MM, Khalil WA, Repp R, Markus M, et al. (2004) Efficient gene delivery with serum into human cancer cells using targeted anionic liposome. J Drug Targeting 12: 11–18.
[42]
Kabiri M, Amiri-Tehranizedeh Z, Baratian Ali, Saberi MR, Chamani J (2012) Use of spectroscopic, zeta potential and molecular dynamic techniques to study the interaction between human holo-transferrin and two antagonist drugs: comparison of binary and ternary systems. Molecules 17: 3114–3147.
[43]
Kopka ML, Yoon C, Goodsell D, Pjura P, Dickerson RE (1985) The molecular origin of DNA-drug specificity in netropsin and distamycin. Proc Natl Acad Sci USA 82: 1376–1380.
[44]
Mukherjee A, Lavery R, Bagchi B, Hynes JT (2008) On the molecular mechanism of drug intercalation into DNA: Asimulation study of the intercalation pathway, free energy, and DNA structural changes. J Am Chem Soc 130: 9747–9755.
