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Modulation of DNA intercalation by resveratrol and genistein

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Abstract

Time correlated Single Photon Counting study (TCSPC) was performed for the first time to evaluate the effect of resveratrol (RES) and genistein (GEN) at 10–100 μM and 10–150 μM respectively, in modulating the DNA conformation and the variation induced due to intercalation by the dyes, ethidium bromide (EtBr) and acridine orange (AO). It is demonstrated using UV-absorption and fluorescence spectroscopy that RES and GEN, at 50 μM and 100 μM respectively can bind to DNA resulting in significant de-intercalation of the dyes, preventing their further intercalation within DNA. Hyperchromicity with red/blue shifts in DNA when bound to dyes was reduced upon addition of RES and GEN. DNA-dependent fluorescence of EtBr and AO was quenched in the presence of RES by 87.97% and 79.13% respectively, while similar quenching effect was observed for these when interacted with GEN (85.52% and 83.85%). It is found from TCSPC analysis that the higher lifetime component or constituent of intercalated dyes (τ2, A 2) decreased with the subsequent increase in smaller component or constituent of free dye (τ1, A 1) after the interaction of drugs with the intercalated DNA. Thus these findings signify that RES and GEN can play an important role in modulating DNA intercalation, leading to the reduction in DNA-directed toxicity.

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References

  • Durr FE, Wallace RE, Citarella RV: Molecular and biochemical pharmacology of mitoxantrone. Cancer Treat Rev 10: 3–11, 1983

    Article  PubMed  Google Scholar 

  • Graves DE, Wadkins RM: 7-Azidoactinomycin D: a novel probe for examining actinomycin D-DNA interactions. J Biol Chem 264: 7262–7266, 1989

    PubMed  CAS  Google Scholar 

  • Goto S, Ihara Y, Urata Y, Izumi S, Abe K, Koji T, Kondo T: Doxorubicin-induced DNA intercalation and scavenging by nuclear glutathione S-transferase π, The FASEB Journal. 15: 2702–2714, 2001

    Article  PubMed  CAS  Google Scholar 

  • Shchyolkina AK, Borisova OF: Stabilizing and destabilizing effects of intercalators on DNA triplexes. FEBS Lett 419: 27–31, 1997

    Article  PubMed  CAS  Google Scholar 

  • Lyles MB, Cameron IL: Caffeine and other xanthines as cytochemical blockers and removers of heterocyclic DNA intercalators from chromatin. Cell Biol Int 26: 145–154, 2002

    Article  PubMed  CAS  Google Scholar 

  • Gao X, Xu YX, Divine G, Janakiraman N, Chapman RA, Gautam SC: Disparate in vitro and in vivo antileukemic effects of resveratrol, a natural polyphenolic compound found in grapes. J Nutr 132: 2076–2081, 2002

    PubMed  CAS  Google Scholar 

  • Delmas D, Passilly-Degrace P, Jannin B, Malki MC, Latruffe N: Resveratrol, a chemopreventive agent, disrupts the cell cycle control of human SW480 colorectal tumor cells. Inter J Mol Med 10: 193–199, 2002

    CAS  Google Scholar 

  • Ahmad A, Asad SF, Singh S, Hadi SM: DNA breakage by resveratrol and Cu (II): reaction mechanism and bacteriophage inactivation. Cancer Lett 154: 29–37, 2000

    Article  PubMed  CAS  Google Scholar 

  • Fukuhara K, Miyata N: Resveratrol as a new type of DNA-cleaving agent. Bioorg Med Chem Lett 8: 87–92, 1998

    Article  Google Scholar 

  • Sun NJ, Woo SH, Cassady IM, Snapka RM: DNA polymerase and topoisomerase II inhibitors from Psoralea corylifolia. J Nat Prod 61: 362–366, 1998

    Article  PubMed  CAS  Google Scholar 

  • Fontecave M, Lepoivre M, Elleingand E, Gerez C, Guittet O: Resveratrol a remarkable inhibitor of ribonucleotide reductase. FEBS Lett 421: 277–279, 1998

    Article  PubMed  CAS  Google Scholar 

  • Sgambato A, Ardito R, Faragila B, Boninsegna A, Wolf FI, Cittadini A: Resveratrol, a natural phenolic compound, inhibits cell proliferation and prevents oxidative DNA damage. Mutat Res 496: 171–180, 2001

    PubMed  CAS  Google Scholar 

  • Elattar TM, Virji AS: The effect of red wine and its components on growth and proliferation of human oral squamous carcinoma cells. Anticancer Res 19: 5407–5414, 1999

    PubMed  CAS  Google Scholar 

  • Nishino H, Aoike A: Genistein arrests cell cycle progression at G2-M. Cancer Res 53: 1328–1331, 1993

    PubMed  Google Scholar 

  • Win W, Cao Z, Peng X, Trush MA, Li Y: Different effects of genistein and resveratrol on oxidative DNA damage in vitro. Mutat Res 513: 113–120, 2002

    PubMed  CAS  Google Scholar 

  • Uenobe F, Nakamura S, Miyazama M: Antimutagenic effect of resveratrol against Trp-P-I. Mutat Res 373: 197–200, 1997

    PubMed  CAS  Google Scholar 

  • Nedeljkovic A, Radulovic S, Bjeldgrlic S: Pleiotropic effect of genistein makes it a promising cancer protecting compound. Archive of Oncol 9: 171–174, 2001

    Google Scholar 

  • Johnson IM, Kumar SGB, Malathi R: De-intercalation of ethidium bromide and acridine orange by xanthine derivatives and their modulatory effect on anticancer agents: a study of DNA-directed toxicity enlightened by time correlated single photon counting. J Biomol Str Dyn 20: 677–686, 2003

    CAS  Google Scholar 

  • Usha S, Johnson IM, Malathi R: Interaction of Resveratrol and Genistein with Nucleic acids. J Biochem Mol Biol 38: 198–205, 2005

    PubMed  CAS  Google Scholar 

  • Baer-Dubowska W, Ignatowicz E, Balana B, Szaefer H: The effect of plant phenolics on the formation of 7,12-dimethyl benz[a]anthracene-DNA adducts and TPA stimulated polymorphonuclear neutrophils chemiluminescence in vitro. Proc Amer Assoc Cancer Res 42: 104, 2001

    Google Scholar 

  • Lee R, Kim YJ, Lee YJ, Chaung HW: The selective effect of genistein on the toxicity of bleomycin in normal lymphocytes and HL-60 cells. Toxicology 195: 87–95, 2004

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600 113, India

    Subbiah Usha & Raghunathan Malathi

  2. Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, 874 Union Avenue, Memphis, Tennessee, 38163, USA

    Irudayam Maria Johnson

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  1. Subbiah Usha
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  2. Irudayam Maria Johnson
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  3. Raghunathan Malathi
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Usha, S., Johnson, I.M. & Malathi, R. Modulation of DNA intercalation by resveratrol and genistein. Mol Cell Biochem 284, 57–64 (2006). https://doi.org/10.1007/s11010-005-9013-6

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  • DOI: https://doi.org/10.1007/s11010-005-9013-6

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