1887

Abstract

Oxyresveratrol is a naturally occurring phytoalexin produced by plants in response to infection. Biological activities of oxyresveratrol have been studied such as antioxidant, anticancer and anti-inflammation. However, further antimicrobial activity and its mechanism need to be investigated. This study exhibited growth inhibition against pathogenic fungi and investigated its mode of action. Oxyresveratrol inflicted cleavage on DNA, leading to G2/M phase arrest. DNA damage by oxyresveratrol was not the result of oxidative stress but it was triggered by direct binding to DNA. Oxyresveratrol-treated cells showed an apoptotic pathway characterized by phosphatidylserine exposure, apoptotic volume decrease and metacaspase activation. Mitochondria-associated apoptotic features also appeared. Oxyresveratrol-induced Ca overload led to mitochondrial membrane depolarization and release of cytochrome c from mitochondria to cytosol. In conclusion, oxyresveratrol with DNA-binding affinity induces DNA cleavage, and eventually leads to mitochondria-mediated apoptosis in Candida albicans.

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2018-07-19
2024-04-20
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References

  1. Papon N, Courdavault V, Clastre M, Bennett RJ. Emerging and emerged pathogenic Candida species: beyond the Candida albicans paradigm. PLoS Pathog 2013; 9:e1003550 [View Article][PubMed]
    [Google Scholar]
  2. Kim J, Sudbery P. Candida albicans, a major human fungal pathogen. J Microbiol 2011; 49:171–177 [View Article][PubMed]
    [Google Scholar]
  3. Khan MSA, Ahmad I, Aqil F, Owais M, Shahid M et al. Virulence and pathogenicity of fungal pathogens with special reference to Candida albicans. Combating Fungal Infections 201021–45
    [Google Scholar]
  4. Sardi JC, Scorzoni L, Bernardi T, Fusco-Almeida AM, Mendes Giannini MJ. Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options. J Med Microbiol 2013; 62:10–24 [View Article][PubMed]
    [Google Scholar]
  5. Berman J. Candida albicans. Curr Biol 2012; 22:R620–R622 [View Article][PubMed]
    [Google Scholar]
  6. Clancy CJ, Nguyen MH. Systemic candidiasis: candidemia and deep-organ infections. Candida and Candidiasis, Second Edition. American Society of Microbiology: 2012 pp. 429–441
    [Google Scholar]
  7. Mishra NN, Prasad T, Sharma N, Payasi A, Prasad R et al. Pathogenicity and drug resistance in Candida albicans and other yeast species. a review. Acta Microbiol Immunol Hung 2007; 54:201–235 [View Article][PubMed]
    [Google Scholar]
  8. Yang YL. Virulence factors of Candida species. J Microbiol Immunol Infect 2003; 36:223–228[PubMed]
    [Google Scholar]
  9. Neto JB, da Silva CR, Neta MA, Campos RS, Siebra JT et al. Antifungal activity of naphthoquinoidal compounds in vitro against fluconazole-resistant strains of different Candida species: a special emphasis on mechanisms of action on Candida tropicalis. PLoS One 2014; 9:e93698 [View Article][PubMed]
    [Google Scholar]
  10. Jeandet P, Delaunois B, Conreux A, Donnez D, Nuzzo V et al. Biosynthesis, metabolism, molecular engineering, and biological functions of stilbene phytoalexins in plants. Biofactors 2010; 36:331–341 [View Article][PubMed]
    [Google Scholar]
  11. Ahuja I, Kissen R, Bones AM. Phytoalexins in defense against pathogens. Trends Plant Sci 2012; 17:73–90 [View Article][PubMed]
    [Google Scholar]
  12. Mert-Türk F. Phytoalexins: defence or just a response to stress. J Cell Mol Biol 2002; 1:1–6
    [Google Scholar]
  13. Parage C, Tavares R, Réty S, Baltenweck-Guyot R, Poutaraud A et al. Structural, functional, and evolutionary analysis of the unusually large stilbene synthase gene family in grapevine. Plant Physiol 2012; 160:1407–1419 [View Article][PubMed]
    [Google Scholar]
  14. Lee SK, Lee HJ, Min HY, Park EJ, Lee KM et al. Antibacterial and antifungal activity of pinosylvin, a constituent of pine. Fitoterapia 2005; 76:258–260 [View Article][PubMed]
    [Google Scholar]
  15. Wu JM, Hsieh TC. Resveratrol: a cardioprotective substance. Ann N Y Acad Sci 2011; 1215:16–21 [View Article][PubMed]
    [Google Scholar]
  16. Plumed-Ferrer C, Väkeväinen K, Komulainen H, Rautiainen M, Smeds A et al. The antimicrobial effects of wood-associated polyphenols on food pathogens and spoilage organisms. Int J Food Microbiol 2013; 164:99–107 [View Article][PubMed]
    [Google Scholar]
  17. Das S, Das DK. Anti-inflammatory responses of resveratrol. Inflamm Allergy Drug Targets 2007; 6:168–173 [View Article][PubMed]
    [Google Scholar]
  18. Lim Y-H, Kim K-H, Kim J-K. Source, biosynthesis, biological activities and pharmacokinetics of oxyresveratrol. Korean J Food Sci Technol 2015; 47:545–555 [View Article]
    [Google Scholar]
  19. Tan H-Y, Tse IMY, Li ETS, Wang M. Inhibitory effects of oxyresveratrol and cyanomaclurin on adipogenesis of 3T3-L1 cells. J Funct Foods 2015; 15:207–216 [View Article]
    [Google Scholar]
  20. Chung KO, Kim BY, Lee MH, Kim YR, Chung HY et al. In-vitro and in-vivo anti-inflammatory effect of oxyresveratrol from Morus alba L. J Pharm Pharmacol 2003; 55:1695–1700 [View Article][PubMed]
    [Google Scholar]
  21. Weber JT, Lamont M, Chibrikova L, Fekkes D, Vlug AS et al. Potential neuroprotective effects of oxyresveratrol against traumatic injury. Eur J Pharmacol 2012; 680:55–62 [View Article][PubMed]
    [Google Scholar]
  22. Joung DK, Mun SH, Choi SH, Kang OH, Kim SB et al. Antibacterial activity of oxyresveratrol against methicillin-resistant Staphylococcus aureus and its mechanism. Exp Ther Med 2016; 12:1579–1584 [View Article][PubMed]
    [Google Scholar]
  23. Chuanasa T, Phromjai J, Lipipun V, Likhitwitayawuid K, Suzuki M et al. Anti-herpes simplex virus (HSV-1) activity of oxyresveratrol derived from Thai medicinal plant: mechanism of action and therapeutic efficacy on cutaneous HSV-1 infection in mice. Antiviral Res 2008; 80:62–70 [View Article][PubMed]
    [Google Scholar]
  24. Basset C, Rodrigues AM, Eparvier V, Silva MR, Lopes NP et al. Secondary metabolites from Spirotropis longifolia (DC) Baill and their antifungal activity against human pathogenic fungi. Phytochemistry 2012; 74:166–172 [View Article][PubMed]
    [Google Scholar]
  25. CLSI Clinical and Laboratory Standards Institute. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts-Third Edition: Approved StandardM27-A3, 3rd ed. vol 28, No 14 Wayne, PA, USA: CLSI; 2008
    [Google Scholar]
  26. Markowska A, Bruzgo M, Gorodkiewicz E, Surażyński A. Synthesis and biological activity of N-sulfonyltripeptides with C-terminal arginine as potential serine proteases inhibitors. Int J Pept Res Ther 2013; 19:191–198 [View Article][PubMed]
    [Google Scholar]
  27. Rahman MA, Bishayee K, Sadra A, Huh SO. Oxyresveratrol activates parallel apoptotic and autophagic cell death pathways in neuroblastoma cells. Biochim Biophys Acta 2017; 1861:23–36 [View Article][PubMed]
    [Google Scholar]
  28. Athar M, Back JH, Kopelovich L, Bickers DR, Kim AL. Multiple molecular targets of resveratrol: anti-carcinogenic mechanisms. Arch Biochem Biophys 2009; 486:95–102 [View Article][PubMed]
    [Google Scholar]
  29. Lee J, Lee DG. Novel antifungal mechanism of resveratrol: apoptosis inducer in Candida albicans. Curr Microbiol 2015; 70:383–389 [View Article][PubMed]
    [Google Scholar]
  30. Paulo L, Ferreira S, Gallardo E, Queiroz JA, Domingues F. Antimicrobial activity and effects of resveratrol on human pathogenic bacteria. World J Microbiol Biotechnol 2010; 26:1533–1538 [View Article]
    [Google Scholar]
  31. Cassone M, Serra P, Mondello F, Girolamo A, Scafetti S et al. Outbreak of Saccharomyces cerevisiae subtype boulardii fungemia in patients neighboring those treated with a probiotic preparation of the organism. J Clin Microbiol 2003; 41:5340–5343 [View Article][PubMed]
    [Google Scholar]
  32. Garzoni C, Nobre VA, Garbino J. Candida parapsilosis endocarditis: a comparative review of the literature. Eur J Clin Microbiol Infect Dis 2007; 26:915–926 [View Article][PubMed]
    [Google Scholar]
  33. Erer B, Galimberti M, Lucarelli G, Giardini C, Polchi P et al. Trichosporon beigelii: a life-threatening pathogen in immunocompromised hosts. Bone Marrow Transplant 2000; 25:745–749 [View Article][PubMed]
    [Google Scholar]
  34. Abdel-Sater MA, Moubasher AA, Soliman Z. Identification of three yeast species using the conventional and internal transcribed spacer region sequencing methods as first or second global record from human superficial infections. Mycoses 2016; 59:652–661 [View Article][PubMed]
    [Google Scholar]
  35. Fukuhara K, Nagakawa M, Nakanishi I, Ohkubo K, Imai K et al. Structural basis for DNA-cleaving activity of resveratrol in the presence of Cu(II). Bioorg Med Chem 2006; 14:1437–1443 [View Article][PubMed]
    [Google Scholar]
  36. Polo SE, Jackson SP. Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes Dev 2011; 25:409–433 [View Article][PubMed]
    [Google Scholar]
  37. Lee Y, Kim K, Kang KT, Lee JS, Yang SS et al. Atmospheric-pressure plasma jet induces DNA double-strand breaks that require a Rad51-mediated homologous recombination for repair in Saccharomyces cerevisiae. Arch Biochem Biophys 2014; 560:1–9 [View Article][PubMed]
    [Google Scholar]
  38. Azzopardi M, Farrugia G, Balzan R. Cell-cycle involvement in autophagy and apoptosis in yeast. Mech Ageing Dev 2017; 161:211–224 [View Article][PubMed]
    [Google Scholar]
  39. O'Connell MJ, Walworth NC, Carr AM. The G2-phase DNA-damage checkpoint. Trends Cell Biol 2000; 10:296–303 [View Article][PubMed]
    [Google Scholar]
  40. Trouiller B, Reliene R, Westbrook A, Solaimani P, Schiestl RH. Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer Res 2009; 69:8784–8789 [View Article][PubMed]
    [Google Scholar]
  41. Salmon TB, Evert BA, Song B, Doetsch PW. Biological consequences of oxidative stress-induced DNA damage in Saccharomyces cerevisiae. Nucleic Acids Res 2004; 32:3712–3723 [View Article][PubMed]
    [Google Scholar]
  42. Honda M, Yamada Y, Tomonaga M, Ichinose H, Kamihira S. Correlation of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, and clinical features of hematological disorders: a pilot study. Leuk Res 2000; 24:461–468 [View Article][PubMed]
    [Google Scholar]
  43. Li L, Sun J, Xia S, Tian X, Cheserek MJ et al. Mechanism of antifungal activity of antimicrobial peptide APP, a cell-penetrating peptide derivative, against Candida albicans: intracellular DNA binding and cell cycle arrest. Appl Microbiol Biotechnol 2016; 100:3245–3253 [View Article][PubMed]
    [Google Scholar]
  44. Opperman TJ, Kwasny SM, Li JB, Lewis MA, Aiello D et al. DNA targeting as a likely mechanism underlying the antibacterial activity of synthetic bis-indole antibiotics. Antimicrob Agents Chemother 2016; 60:7067–7076 [View Article][PubMed]
    [Google Scholar]
  45. Walles SA. Mechanisms of DNA damage induced in rat hepatocytes by quinones. Cancer Lett 1992; 63:47–52 [View Article][PubMed]
    [Google Scholar]
  46. Roos WP, Kaina B. DNA damage-induced cell death by apoptosis. Trends Mol Med 2006; 12:440–450 [View Article][PubMed]
    [Google Scholar]
  47. Keyhani E, Khavari-Nejad S, Keyhani J, Attar F. Acriflavine-mediated apoptosis and necrosis in yeast Candida utilis. Ann N Y Acad Sci 2009; 1171:284–291 [View Article][PubMed]
    [Google Scholar]
  48. Sun X, Li Y, Li W, Zhang B, Wang AJ et al. Selective induction of necrotic cell death in cancer cells by β-lapachone through activation of DNA damage response pathway. Cell Cycle 2006; 5:2029–2035 [View Article][PubMed]
    [Google Scholar]
  49. Madeo F, Herker E, Wissing S, Jungwirth H, Eisenberg T et al. Apoptosis in yeast. Curr Opin Microbiol 2004; 7:655–660 [View Article][PubMed]
    [Google Scholar]
  50. Hankins HM, Baldridge RD, Xu P, Graham TR. Role of flippases, scramblases and transfer proteins in phosphatidylserine subcellular distribution. Traffic 2015; 16:35–47 [View Article][PubMed]
    [Google Scholar]
  51. Segawa K, Nagata S. An apoptotic ‘eat me’ signal: phosphatidylserine exposure. Trends Cell Biol 2015; 25:639–650 [View Article][PubMed]
    [Google Scholar]
  52. Hao B, Cheng S, Clancy CJ, Nguyen MH. Caspofungin kills Candida albicans by causing both cellular apoptosis and necrosis. Antimicrob Agents Chemother 2013; 57:326–332 [View Article][PubMed]
    [Google Scholar]
  53. Julian L, Olson MF. Apoptotic membrane dynamics in health and disease. Cell Health Cytoskele 2015; 2015:133–142
    [Google Scholar]
  54. Hill SM, Nyström T. The dual role of a yeast metacaspase: what doesn't kill you makes you stronger. Bioessays 2015; 37:525–531 [View Article][PubMed]
    [Google Scholar]
  55. Carmona-Gutierrez D, Eisenberg T, Büttner S, Meisinger C, Kroemer G et al. Apoptosis in yeast: triggers, pathways, subroutines. Cell Death Differ 2010; 17:763–773 [View Article][PubMed]
    [Google Scholar]
  56. Mazzoni C, Falcone C. Caspase-dependent apoptosis in yeast. Biochim Biophys Acta 1783; 2008:1320–1327
    [Google Scholar]
  57. Olofsson MH, Havelka AM, Brnjic S, Shoshan MC, Linder S. Charting calcium-regulated apoptosis pathways using chemical biology: role of calmodulin kinase II. BMC Chem Biol 2008; 8:2 [View Article][PubMed]
    [Google Scholar]
  58. Smaili SS, Hsu YT, Carvalho AC, Rosenstock TR, Sharpe JC et al. Mitochondria, calcium and pro-apoptotic proteins as mediators in cell death signaling. Braz J Med Biol Res 2003; 36:183–190 [View Article][PubMed]
    [Google Scholar]
  59. Zorova LD, Popkov VA, Plotnikov EY, Silachev DN, Pevzner IB et al. Mitochondrial membrane potential. Anal Biochem 2018; 552: [View Article][PubMed]
    [Google Scholar]
  60. Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev 2007; 87:99–163 [View Article][PubMed]
    [Google Scholar]
  61. Eisenberg T, Büttner S, Kroemer G, Madeo F. The mitochondrial pathway in yeast apoptosis. Apoptosis 2007; 12:1011–1023 [View Article][PubMed]
    [Google Scholar]
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