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Cytotechnology

, Volume 67, Issue 6, pp 939–946 | Cite as

Cytotoxicity and genotoxicity of zingiberene on different neuron cell lines in vitro

  • Basak Togar
  • Hasan Turkez
  • Abdulgani Tatar
  • Ahmet Hacimuftuoglu
  • Fatime Geyikoglu
Brief Report

Abstract

The main objective of this study is to investigate the cytotoxic, genotoxic and antioxidant properties of zingiberene (ZBN) in an in vitro rat brain cell culture study. The cytotoxic effect was determined against the rat neuron and N2a neuroblastoma (N2a-NB) cell lines using the 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while the antioxidant activity was assessed using the total antioxidant capacity (TAC) and total oxidative stress (TOS) assays. The effects on DNA damage were also evaluated in this study by the single cell gel electrophoresis assay. The results indicated that ZBN has an anti-proliferative activity suppressing the proliferation of N2a-NB cells at concentrations over 50 mg L−1 and neuron cells at concentrations over 150 mg L−1. In addition, ZBN treatments at higher doses (≤50 mg L−1) led to increases of TOS levels in N2a-NB cell cultures. However 25 mg L−1 of ZBN treatment caused increases of TAC levels in cultured neuron and N2a-NB cell cultures while ZBN at doses of 10–400 mg L−1 did not increase the number of total damage score in both cell lines. This study clearly indicates that ZBN has a significant potential to be used as a natural anticancer agent in cultured N2a-NBs.

Keywords

Zingiberene N2a neuroblastoma Total oxidative stress Total antioxidant capacity MTT assay Single cell gel electrophoresis 

Notes

Acknowledgments

This work was supported by the Scientific & Technological Research Council of Turkey (TÜBİTAK, Project Number: 210T142).

References

  1. Abolaji AO, Eteng MU, Omonua O, Adenrele Y (2013) Influence of coadministration of artemether and lumefantrine on selected plasma biochemical and erythrocyte oxidative stress indices in female Wistar rats. Hum Exp Toxicol 32:206–215CrossRefGoogle Scholar
  2. Afoulous S, Ferhout H, Raoelison EG, Valentin A, Moukarzel B, Couderc F, Bouajila J (2013) Chemical composition and anticancer, antiinflammatory, antioxidant and antimalarial activities of leaves essential oil of Cedrelopsis grevei. Food Chem Toxicol 56:352–362CrossRefGoogle Scholar
  3. Agullo G, Gamet-Payrastre L, Manenti S, Viala C, Remesy C, Chap H, Payrastre B (1997) Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: a comparison with tyrosine kinase and protein kinase c inhibition. Biochem Pharmacol 53:1649–1657CrossRefGoogle Scholar
  4. Al-Zubairi AS, Abdul AB, Syam MM (2010) Evaluation of the genotoxicity of zerumbone in cultured human peripheral blood lymphocytes. Toxicol In Vitro 24:707–712CrossRefGoogle Scholar
  5. Anter J, Romero-Jiménez M, Fernández-Bedmar Z, Villatoro-Pulido M, Analla M, Alonso-Moraga A, Muñoz-Serrano A (2011) Antigenotoxicity, cytotoxicity, and apoptosis induction by apigenin, bisabolol, and protocatechuic acid. J Med Food 14:276–283CrossRefGoogle Scholar
  6. Antonious GF, Kochhar TS (2003) Zingiberene and curcumene in wild tomato. J Environ Sci Health B 38:489–500CrossRefGoogle Scholar
  7. Awad WA, Ghareeb K, Dadak A, Gille L, Staniek K, Hess M, Böhm J (2012) Genotoxic effects of deoxynivalenol in broiler chickens fed low-protein feeds. Poult Sci 91:550–555CrossRefGoogle Scholar
  8. Aydın E, Turkez H, Keles MS (2014) The effect of carvacrol on healthy neurons and N2a cancer cells: some biochemical, anticancerogenicity and genotoxicity studies. Cytotechnology 66:149–157CrossRefGoogle Scholar
  9. Ban JY, Jeon SY, Nguyen TT, Bae K, Song KS, Seong YH (2006) Neuroprotective effect of oxyresveratrol from smilacis chinae rhizome on amyloid β protein (25-35)-induced neurotoxicity in cultured rat cortical neurons. Biol Pharm Bull 29:2419–2424CrossRefGoogle Scholar
  10. Ben Ammar R, Bhouri W, Ben Sghaier M, Boubaker J, Skandrani I, Neffati A, Chekir-Ghedira L, Ghedira K (2009) Antioxidant and free radical-scavenging properties of three flavonoids isolated from the leaves of Rhamnus alaternus L. (Rhamnaceae): a structure–activity relationship study. Food Chem 116:258–264CrossRefGoogle Scholar
  11. Ben Sghaıer M, Skandrani I, Nasr N, Franca MG, Chekir-Ghedira L, Ghedira K (2011) Flavonoids and sesquiterpenes from Tecurium ramosissimum Promote antiproliferation of human cancer cells and enhance antioxidant activity: a structure–activity relationship study. Environ Toxicol Pharmacol 32:336–348CrossRefGoogle Scholar
  12. Boopathy NS, Kathiresan K (2010) Anticancer drugs from marine flora: an overview. J Oncol 2010:214186Google Scholar
  13. Bou DD, Lago JH, Figueiredo CR, Matsuo AL, Guadagnin RC, Soares MG, Sartorelli P (2013) Chemical composition and cytotoxicity evaluation of essential oil from leaves of Casearia sylvestris, its main compound α-zingiberene and derivatives. Molecules 18:9477–9487CrossRefGoogle Scholar
  14. Brodeur GM (2003) Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 3:203–216CrossRefGoogle Scholar
  15. Brusselmans K, Vrolix R, Verhoeven G, Swinnen JV (2005) Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. J Biol Chem 280:5636–5645CrossRefGoogle Scholar
  16. Chaudhary SC, Alam MS, Siddiqui MS, Athar M (2009) Chemopreventive effect of farnesol on DMBA/TPA-induced skin tumorigenesis: involvement of inflammation, Ras-ERK pathway and apoptosis. Life Sci 85:196–205CrossRefGoogle Scholar
  17. Chen ZP, Schell JB, Ho CT, Chen KY (1998) Green Tea Epigallocatechin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts. Cancer Lett 129:173–179CrossRefGoogle Scholar
  18. Chen D, Daniel KG, Chen MS, Kuhn DJ, Landis-Piwowar KR, Dou QP (2005) Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells. Biochem Pharmacol 69:1421–1432CrossRefGoogle Scholar
  19. Constantinou A, Mehta R, Runyan C, Rao K, Vaughan A, Moon R (1995) Flavonoids as DNA topoisomerase antagonists and poisons: structure–activity relationships. J Nat Prod 58:217–225CrossRefGoogle Scholar
  20. Davıs ME, Croteau R (2000) Cyclization enzymes in the biosynthesis of monoterpenes, sesquiterpenes, and diterpenes topics in current. Top Curr Chem 209:54–92Google Scholar
  21. Denyer CV, Jackson P, Loakes DMJ (1994) Isolation of antirhinoviral sesquiterpenes from ginger (Zingiber officinale). Nat Prod 57:658–662CrossRefGoogle Scholar
  22. Di Sotto A, Mazzanti G, Carbone F, Hrelia P, Maffei F (2010) Inhibition by beta-caryophyllene of ethyl methanesulfonate-induced clastogenicity in cultured human lymphocytes. Mutat Res 699:23–28CrossRefGoogle Scholar
  23. Erel O (2004) A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 37:277–285CrossRefGoogle Scholar
  24. Erel O (2005) A new automated colorimetric method for measuring total oxidant status. Clin Biochem 38:1103–1111CrossRefGoogle Scholar
  25. Hamułka J, Wawrzyniak A, Sulich A (2012) The assessment of beta-carotene, lycopene and lutein intake selected group of adults. Rocz Panstw Zakl Hig 63:179–185Google Scholar
  26. Iranshahi M, Sahebkar A, Takasaki M, Konoshima T, Tokuda H (2009) Cancer chemopreventive activity of the prenylated coumarin, umbelliprenin, in vivo. Eur J Cancer Prev 18:412–415CrossRefGoogle Scholar
  27. Jeena K, Liju VB, Kuttan R (2011) A preliminary 13-week oral toxicity study of ginger oil in male and female Wistar rats. Int J Toxicol 30:662–670CrossRefGoogle Scholar
  28. Kazi A, Wang Z, Kumar N, Falsetti SC, Chan TH, Dou QP (2004) Structure activity relationships of synthetic analogs of (−)-epigallocatechin-3-gallate as proteasome inhibitors. Anticancer Res 24:943–954Google Scholar
  29. Kilani-Jaziri S, Neffati A, Limem I, Boubaker J, Skandrani I, Ben Sghaier M, Bouhlel I, Bhouri W, Mariotte AM, Ghedira K, Dijoux-Franca MG, Chekir-Ghedira L (2009) Relationship correlation of antioxidant and antiproliferative capacity of Cyperus rotundus products towards K562. Chem Biol Interact 181:85–94CrossRefGoogle Scholar
  30. Kundu A, Saha S, Walia S, Shakil NA, Kumar J, Annapurna K (2013) Cadinene sesquiterpenes from Eupatorium adenophorum and their antifungal activity. J Environ Sci Health B 48:516–522CrossRefGoogle Scholar
  31. Kusano C, Ferrari B (2008) Total antioxidant capacity: a biomarker in biomedical and nutritional studies. J Cell Mol Biol 7:1–15Google Scholar
  32. Lepley DM, Li B, Birt DF, Pelling JC (1996) The Chemopreventive flavonoid apigenin induces g2/m arrest in keratinocytes. Carcinogenesis 17:2367–2375CrossRefGoogle Scholar
  33. Lewerenz V, Hanelt S, Nastevska C, El-Bahay C, Rouhrdanz E, Kahl R (2003) Antioxidants protect primary rat hepatocyte cultures against acetaminophen-induced DNA strand breaks but not against acetaminophen induced cytotoxicity. Toxicology 191:179–187CrossRefGoogle Scholar
  34. Millar JG (1998) Rapid and simple isolation of zingiberene from ginger essential oil. J Nat Prod 61:1025–1026CrossRefGoogle Scholar
  35. Mishima S, Ono Y, Araki Y, Akao Y, Nozawa Y (2005) Two related cinnamic acid derivatives from Brazilian honey bee propolis, baccharin and drupanin, induce growth inhibition in allografted sarcoma S-180 in mice. Biol Pharm Bull 28:1025–1030CrossRefGoogle Scholar
  36. Ozkan D, Yüzbaşıoğlu D, Unal F, Yılmaz S, Aksoy H (2009) Evaluation of the cytogenetic damage induced by the organophosphorous insecticide acephate. Cytotechnology 59:73–80CrossRefGoogle Scholar
  37. Parada-Turska J, Paduch R, Majdan M, Kandefer-Szerszeń M, Rzeski W (2007) Antiproliferative activity of parthenolide against three human cancer cell lines and human umbilical vein endothelial cells. Pharmacol Rep 59:233–237Google Scholar
  38. Plaumann B, Fritsche M, Rimpler H, Brandner G, Hess RD (1996) Flavonoids activate wild-type p53. Oncogene 13:1605–1614Google Scholar
  39. Ranković BR, Kosanić MM, Stanojković TP (2011) Antioxidant, antimicrobial and anticancer activity of the lichens Cladonia furcata, Lecanora atra and Lecanora muralis. BMC Complement Altern Med 20:11–97Google Scholar
  40. Scalcinati G, Partow S, Siewers V, Schalk M, Daviet L, Nielsen J (2012) Combined metabolic engineering of precursor and co-factor supply to increase α-santalene production by Saccharomyces cerevisiae. Microb Cell Fact 11:117CrossRefGoogle Scholar
  41. Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191CrossRefGoogle Scholar
  42. Stiller CA, Parkin DM (1992) International variations in the incidence of neuroblastoma. Int J Cancer 52:538–543CrossRefGoogle Scholar
  43. Styrczewska M, Kulma A, Kostyn K, Hasiewicz-Derkacz K, Szopa J (2012) Flax terpenoid pathway as a source of health promoting compounds. Mini Rev Med Chem 13:353–364Google Scholar
  44. Svensson K, Larsson C (2003) A protein kinase Cbeta inhibitor attenuates multidrug resistance of neuroblastoma cells. BMC Cancer 26:3–10Google Scholar
  45. Sylvester PW (2011) Optimization of the tetrazolium dye (MTT) colorimetric assay for cellular growth and viability. Methods Mol Biol 716:157–168CrossRefGoogle Scholar
  46. Taha MM, Abdul AB, Abdullah R, Ibrahim TA, Abdelwahab SI, Mohan S (2010) Potential chemoprevention of diethylnitrosamine-initiated and 2-acetylaminofluorene-promoted hepatocarcinogenesis by zerumbone from the rhizomes of the subtropical ginger (Zingiber zerumbet). Chem Biol Interact 86:295–305CrossRefGoogle Scholar
  47. Turkez H, Aydin E, Aslan A (2012a) Xanthoria elegans (Link) (lichen) extract counteracts DNA damage and oxidative stress of mitomycin C in human lymphocytes. Cytotechnology 64:679–686CrossRefGoogle Scholar
  48. Turkez H, Geyikoglu F, Mokhtar YI, Togar B (2012b) Eicosapentaenoic acid protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced hepatic toxicity in cultured rat hepatocytes. Cytotechnology 64:15–25CrossRefGoogle Scholar
  49. Turkez H, Togar B, Polat E (2012c) Olive leaf extract modulates permethrin induced genetic and oxidative damage in rats. Cytotechnology 64:459–464CrossRefGoogle Scholar
  50. Wang Q, Wu LM, Li AY, Zhao Y, Wang NP (2001) Experimental studies of antitumor effect of artesunate on liver cancer. Zhongguo Zhong Yao Za Zhi 26:707–728Google Scholar
  51. Wang YL, Li RP, Guo ML, Zhang G, Zhang N, Ma YL (2009) Bakkenolides from Petasites tricholobus and their neuroprotective effects related to antioxidant activities. Planta Med 75:230–235CrossRefGoogle Scholar
  52. Wang H, Wang Y, Liu P, Wang W, Fan Y, Zhu W (2013) Purpurides B and C, two new sesquiterpene esters from the aciduric fungus Penicillium purpurogenum JS03-21. Chem Biodivers 10:1185–1192CrossRefGoogle Scholar
  53. Wassberg E, Hedborg F, Sköldenberg E, Stridsberg M, Christofferson R (1999) Inhibition of angiogenesis induces chromaffin differentiation and apoptosis in neuroblastoma. Am J Pathol 154:395–403CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Basak Togar
    • 1
  • Hasan Turkez
    • 2
  • Abdulgani Tatar
    • 3
  • Ahmet Hacimuftuoglu
    • 4
  • Fatime Geyikoglu
    • 1
  1. 1.Department of Biology, Faculty of ScienceAtatürk UniversityErzurumTurkey
  2. 2.Department of Molecular Biology and Genetics, Faculty of SciencesErzurum Technical UniversityErzurumTurkey
  3. 3.Department of Medical Genetics, Faculty of MedicalAtatürk UniversityErzurumTurkey
  4. 4.Department of Medical Pharmacology, Faculty of MedicalAtatürk UniversityErzurumTurkey

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