Anticancer and Antioxidant Properties of Terpinolene in Rat Brain Cells

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Terpinolene (TPO) is a natural monoterpene present in essential oils of many aromatic plant species. Although various biological activities of TPO have been demonstrated, its neurotoxicity has never been explored. In this in vitro study we investigated TPO’s antiproliferative and/or cytotoxic properties using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test, genotoxic damage potential using the single-cell gel electrophoresis (SCGE), and oxidative effects through total antioxidant capacity (TAC) and total oxidative stress (TOS) in cultured primary rat neurons and N2a neuroblastoma cells. Dose-dependent effects of TPO (at 10 mg L-1, 25 mg L-1, 50 mg L-1, 100 mg L-1, 200 mg L-1, and 400 mg L-1) were tested in both cell types. Significant (P<0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the dose of 100 mg L-1 and in N2a neuroblastoma cells starting with 50 mg L-1. TPO was not genotoxic in either cell type. In addition, TPO treatment at 10 mg L-1, 25 mg L-1, and 50 mg L-1 increased TAC in primary rat neurons, but not in N2a cells. However, at concentrations above 50 mg L-1 it increased TOS in both cell types. Our findings clearly demonstrate that TPO is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.

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  • 1. Maidment SL Pilkington GJ. Brain Cancers. In: Encyclopaedia of Life Sciences. Nature Publishing Group/MacMillan 2001 (Invited Reference Work for Electronic Publication) doi: 10.1038/npg.els.0001892

  • 2. Clarke MF. Neurobiology: At the root of brain cancer. Nature 2004;432:281-2. doi:10.1038/432281a

  • 3. Maris JM Matthay KK. Molecular biology of neuroblastoma. J Clin Oncol 1999;17:2264-79. PMID: 10561284

  • 4. Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 2003;3:203-16. PMID: 12612655

  • 5. Heck JE Ritz B Hung RJ Hashibe M Boffetta P. The epidemiology of neuroblastoma: a review. Paediatr Perinat Epidemiol 2009;23:125-43. doi: 10.1111/j.1365-3016.2008.00983.x

  • 6. Mueller WP Coppenrath E Pfluger T. Nuclear medicine and multimodality imaging of pediatric neuroblastoma. Pediatr Radiol 2013;43:418-27. doi: 10.1007/s00247-012-2512-1

  • 7. Kang J Kamal A Burrows FJ Evers BM Chung DH. Inhibition of neuroblastoma xenograft growth by Hsp90 inhibitors. Anticancer Res 2006;26:1903-8. PMID: 16827123

  • 8. Bayrak O Seckiner I Erturhan S Aydin A Yagci F. Adult intrarenal neuroblastoma presenting as renal cell carcinoma. Can Urol Assoc J 2012;6:E144-6. doi: 10.5489/cuaj.11119

  • 9. Tang CK Hajdu SI. Neuroblastoma in adolescence and adulthood. NY State J Med 1975;75:1434-8. PMID: 1057061

  • 10. Dosik GM Rodriguez V Benjamin RS Bodey GP. Neuroblastoma in the adult: effective combination chemotherapy. Cancer 1978;41:56-63. PMID: 626943

  • 11. Lopez R Karakousis C Rao U. Treatment of adult neuroblastoma. Cancer 1980;45:840-4.

  • 12. Grubb BP Thant M. Neuroblastoma in an adult. Southern Med J 1984;77:1180-2. PMID: 6484689

  • 13. Aleshire SL Glick AD Cruz VE Bradley CA Parl FF. Neuroblastoma in adults. Pathologic findings and clinical outcome. Arch Pathol Lab Med 1985;109:352-6. PMID: 3885899

  • 14. Kaye JA Warhol MJ Kretschmar C Landsberg L Frei E 3rd. Neuroblastoma in adults. Three case reports and a review of the literature. Cancer 1986;58:1149-57. PMID: 3731041

  • 15. Allan SG Cornbleet MA Carmicael J Arnott SJ Smyth JF. Adult neuroblastoma: report of three cases and review of the literature. Cancer 1986;57:2419-21. PMID: 3697939

  • 16. Prestidge BR Donaldson SS. Treatment results among adults with childhood tumors: a 20-year experience. Int J Radiat Oncol Biol Phys 1989;17:507-14. PMID: 2550396

  • 17. Cadet JL Brannock C. Free radicals and the pathobiology of brain dopamine systems. Neurochem Int 1989;32:117-31. PMID: 9542724

  • 18. Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem 2006;97:1634-58. doi: 10.1111/ j.1471-4159.2006.03907.x

  • 19. Mecocci P Mac Garvey U Beal MF. Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease. Ann Neurol 1994;36:747-51. doi: 10.1002/ana.410360510

  • 20. Turkez H Geyikoğlu F Tatar A Keleş S Ozkan A. Effects of some boron compounds on peripheral human blood. Z Naturforsch C 2007;62:889-96. PMID: 18274294

  • 21. Turkez H Geyikoglu F. The effect of laurel leaf extract against toxicity induced by 2378-tetrachlorodibenzo-pdioxin in cultured rat hepatocytes. Arh Hig Rada Toksikol 2011;62:309-15. doi: 10.2478/10004-1254-62-2011-2118

  • 22. Turkez H Aydin E. Anti-genotoxic role of eicosapentaenoic acid against imazalil-induced DNA damage in vitro. Toxicol Ind Health 2012 Feb 8. [Epub ahead of print] doi: 10.1177/0748233711433943

  • 23. Turkez H Geyikoğlu F Dirican E Tatar A. In vitro studies on chemoprotective effect of borax against aflatoxin B1- induced genetic damage in human lymphocytes. Cytotechnology 2012;64:607-12. doi: 10.1007/s10616-012-9454-1

  • 24. Turkez H Aydin E. The effects of taurine on permethrin induced cytogenetic and oxidative damage in cultured human lymphocytes. Arh Hig Rada Toksikol 2012;63:27-34. doi: 10.2478/10004-1254-63-2012-2114

  • 25. Shon MY Choi SD Kahng GG Nam SH Sung NJ. Antimutagenic antioxidant and free radical scavenging activity of ethyl acetate extracts from white yellow and red onions. Food Chem Toxicol 2004;42:659-66. PMID: 15019191

  • 26. Sevgiler Y Karaytug S Karayakar F. Antioxidative effects of N-acetylcysteine lipoic acid taurine and curcumin in the muscle of Cyprinus carpio L. exposed to cadmium. Arh Hig Rada Toksikol 2011;62:1-9. doi: 10.2478/10004-1254-62-2011-2082

  • 27. Charles DJ Simon JE. Comparison of extraction methods for the rapid determination of essential oil content and composition of basil. J Am Soc Hort Sci 1990;115:458-62.

  • 28. Loza-Tavera H. Monoterpenes in essential oils. Biosynthesis and properties. Adv Exp Med Biol 1999;464:49-62. PMID: 10335385

  • 29. Carnesecchi S Schneider Y Ceraline J Duranton B Gosse F Seiler N Raul F. Geraniol a component of plant essential oils inhibits growth and polyamine biosynthesis in human colon cancer cells. J Pharmacol Exp Ther 2001;298:197-200. PMID: 11408542

  • 30. Southwell IA Stiff IA Brophy JJ. Terpinolene varieties of Melaleuca. J Essent Oil Res 1992;4:363-7. doi: 10.1080/10 412905.1992.9698086

  • 31. Burdock GA. Fenaroli’s Hanbook of Flavor Ingredients: Adapted from the Italian Language Works of Giovanni Fenaroli. 3rd ed. Boca Raton: CRC Press; 1995.

  • 32. Brauss MS Linforth RST Cayeux I Harvey B Taylor AJ. Altering the fat content affects fl avor release in a model yogurt system. J Agric Food Chem 1999;47:2055-9. PMID: 10552495

  • 33. Harada T Harada E Sakamoto R Ashitani T Fujita K Kuroda K. Regio- and substrate-specific oxidative metabolism of terpinolene by cytochrome P450 monooxygenases in Cupressus lusitanica cultured cells. Am J Plant Sci 2012;3:268-75. doi: 10.4236/ajps.2012.32032

  • 34. Dorman HJD Figueiredo AC Barroso JG Deans SG. Invitro evaluation of antioxidant activity of essential oils and their components. Flavour Fragr J 2000;15:12-6.

  • 35. Hammer KA Carson CF Riley TV. Antifungal effects of Melaleuca alternifolia (tea tree) oil and its components on Candida albicansCandida glabrata and Saccharomycescerevisiae. J Antimicrob Chemother 2004;53:1081-5. doi: 10.1093/jac/dkh243

  • 36. Conti B Benelli G Flamini G Cioni PL Profeti R Ceccarini L Macchia M Canale A. Larvicidal and repellent activity of Hyptis suaveolens (Lamiaceae) essential oil against the mosquito Aedes albopictus Skuse (Diptera: Culicidae). Parasitol Res 2012;110:2013-21. doi: 10.1007/s00436-011-2730-8

  • 37. Arunasree KM. Anti-proliferative effects of carvacrol on a human metastatic breast cancer cell line MDA-MB 231. Phytomedicine 2010;17:581-8. doi: 10.1016/j. phymed.2009.12.008

  • 38. Wang W Li N Luo M Zu Y Efferth T. Antibacterial activity and anticancer activity of Rosmarinus officinalis L. essential oil compared to that of its main components. Molecules 2012;17:2704-13. doi: 10.3390/molecules17032704

  • 39. Anonymous. National Institute of Health Principles of Laboratory Animal Care USA. 1985;23:1-112.

  • 40. Daikhin Y Yudkoff M. Compartmentation of brain glutamate metabolism in neurons and glia. J Nutr 2000;130(4S Suppl):1026S-31S. PMID: 10736375

  • 41. Zhou JY Tang FD Mao GG Bian RL. Effect of alpha-pinene on nuclear translocation of NF-kappa B in THP-1 cells. Acta Pharmacol Sin 2004;25:480-4. PMID: 15066217

  • 42. Yu Z Wang W Xu L Dong J Jing Y. d-Limonene and dcarvone induce apoptosis in HL-60 cells through activation of caspase-8. Asian J Trad Med 2008;3:134-43.

  • 43. Buyukleyla M Rencuzogullari E. The effects of thymol on sister chromatid exchange chromosome aberration and micronucleus in human lymphocytes. Ecotoxicol Environ Saf 2009;72:943-7. doi: 10.1016/j.ecoenv.2008.10.005

  • 44. Aristatile B Al-Numair KS Al-Assaf AH Pugalendi KV. Pharmacological effect of carvacrol on D: -galactosamineinduced mitochondrial enzymes and DNA damage by singlecell gel electrophoresis J Nat Med 2011;65:568-77. doi: 10.1007/s11418-011-0544-8

  • 45. Singh DK Lippman SM. Cancer chemoprevention part 1: retinoids and carotenoids and other classic antioxidants. Oncology 1998;12:1643-60. PMID: 9834941

  • 46. Kizilian N Wilkins RC Reinhardt P Ferrarotto C McLean JR McNamee JP. Silver stained comet assay for detection of apoptosis. Biotechniques 1999;27:926-30. PMID: 10572638

  • 47. Tice RR Agurell E Anderson D. Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 2000;35:206-21. PMID: 10737956

  • 48. Saleha Banu B Dana Devi K Mahboob M. In vivo genotoxic effect of zinc sulfate in mouse peripheral blood leukocytes using comet assay. Drug Chem Toxicol 2000;24:63-73. doi: 10.1081/DCT-100103086

  • 49. Heaton PR Ransley R Charlton CJ. Application of single-cell gel electrophoresis (comet) assay for assessing levels of DNA damage in canine and feline leukocytes. J Nutr 2002;132(6 Suppl 2):1598S-603S. PMID: 12042468

  • 50. Das GP Shaik AP Jamil K. Cytotoxicity and genotoxicity induced by the pesticide profenofos on cultured human peripheral blood lymphocytes. Drug Chem Toxicol 2006;29:313-22. doi: 10.1080/01480540600653093

  • 51. Turkez H. The role of ascorbic acid on titanium dioxideinduced genetic damage assessed by the comet assay and cytogenetic tests. Exp Toxicol Pathol 2011;63:453-7. doi: 10.1016/j.etp.2010.03.004

  • 52. Todoriki S Hasan M Miyanoshita A Imamura T Hayashi T. Assessment of electron beam-induced DNA damage in larvae of chestnut weevil Curculio sikkimensis (Heller) (Coleoptera: Curculionidae) using comet assay. Radiat Physic C h e m 7 5 ; 2 0 0 6 : 2 9 2 - 6 . d o i : 1 0 . 1 0 1 6 / j . radphyschem.2005.08.001

  • 53. Aydın E Turkez H Keleş MS. The effect of carvacrol on healthy neurons and N2a cancer cells: some biochemical anticancerogenicity and genotoxicity studies. Cytotechnology 2013; (in press) doi: 10.1007/s10616-013-9547-5.

  • 54. Kusano C Ferrari B. Total antioxidant capacity: a biomarker in biomedical and nutritional studies. J Cell Mol Biol 2008;7:1-15.

  • 55. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004;37:112-9. doi: 10.1016/j. clinbiochem.2003.10.014

  • 56. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103-11. doi: 10.1016/j.clinbiochem.2005.08.008

  • 57. Falk AA Hagberg MT Lof AE Wigaeus-Hjelm EM Zhiping W. Uptake distribution and elimination of alpha-pinene in man after exposure by inhalation. Scand J Work Environ Health 1990;16:372-8. doi: 10.5271/sjweh.1771

  • 58. Igimi H Nishimura M. Studies on the metabolism of d-limonene (p-Mentha-18-diene). I. The absorption distribution and excretion of d-limonene in rats. Xenobiotica 1974;4:77-84. doi: 10.3109/00498257409049347

  • 59. Foley WJ Lassak EV Brophy J. Digestion and absorption of Eucalyptus essential oils in greater glider (Petauroidesvolans) and brushtail possums (Trichosurus vulpecula). J Chem Ecol 1987;13:2115-30. doi: 10.1007/BF01012875

  • 60. Boyle R McLean S Foley WJ Davies NW. Comparative metabolism of dietary terpene p-cymene in generalist and specialist folivorous marsupials. J Chem Ecol 1999;25:2109-27. doi: 10.1023/A:1021092908058

  • 61. Boyle R McLean S Davies NW. Biotransformation of 18-cineole in the brushtail possum (Trichosurus vulpecula). Xenobiotica 2000;30:915-32. PMID: 11055269

  • 62. Crowell PL. Prevention and therapy of cancer by dietary monoterpenes. J Nutr 1999;129:775S-8S. PMID: 10082788

  • 63. Crowell PL Lin S Vedejs E Gould MN. Identification of metabolites of the antitumor agent d-limonene capable of inhibiting protein isoprenylation and cell growth. Cancer Chemother Pharmacol 1992;31:205-12. doi: 10.1007/ BF00685549

  • 64. Crowell PL Ren Z Lin S Vedejs E Gould MN. Structureactivity relationships among monoterpene inhibitors of protein isoprenylation and cell proliferation. Biochem Pharmacol 1994;47:1405-15. doi: 10.1016/0006-2952(94)90341-7

  • 65. Kodama R Yano T Furukawa K Noda K Ide H. Studies on the metabolism of d-limonene (p-mentha-18-diene). IV: Isolation and characterization of new metabolites and species differences in metabolism. Xenobiotica 1976;6:377-89. doi: 10.3109/00498257609151649

  • 66. Regan JW Bjeldanes LF. Metabolism of (+)-limonene in rats. J Agric Food Chem 1976;24:377-80. doi: 10.1021/ jf60204a031

  • 67. Yeruva L Pierre KJ Elegbede A Wang RC Carper SW. Perillyl alcohol and perillic acid induced cell cycle arrest and apoptosis in non small cell lung cancer cells. Cancer Letters 2007;257:216-26. doi: 10.1016/j.canlet.2007.07.020

  • 68. Pratheeshkumar P Raphael TJ Kuttan G. Protective role of perillic acid against radiation-induced oxidative stress cytokine profile DNA damage and intestinal toxicity in mice. J Environ Pathol Toxicol Oncol 2010;29:199-212. PMID: 21303327

  • 69. Ma Y Marston G. Formation of organic acids from the gasphase ozonolysis of terpinolene. Phys Chem Chem Phys 2009;11:4198-209. doi: 10.1039/B818789D

  • 70. Okumura N Yoshida H Nishimura Y Kitagishi Y Matsuda S. Terpinolene a component of herbal sage downregulates AKT1 expressionin K562 cells. Oncol Lett 2012;3:321-4. doi: 10.3892/ol.2011.491

  • 71. Silva SL Figueiredo PM Yano T. Cytotoxic evaluation of essential oil from Zanthoxylum rhoifolium Lam. leaves. Acta Amaz 2007;37:281-6. doi: 10.1590/S0044-59672007000200015

  • 72. Rabi T Bishayee A. d-Limonene sensitizes docetaxel-induced cytotoxicity in human prostate cancer cells: Generation of reactive oxygen species and induction of apoptosis. J Carcinog 2009;8:9. doi: 10.4103/1477-3163.51368

  • 73. Rassouli FB Matin MM Iranshahi M Bahrami AR. Investigating the cytotoxic and apoptosis inducing effects of monoterpenoid stylosin in vitro. Fitoterapia 2011;82:742-9. doi: 10.1016/j.fitote.2011.03.005

  • 74. Chen F Kim HJ Wang X Wu C Chung HY Jin Z. Evaluation of antioxidant and antiproliferative activities of tea tree (Melaleuca alternifolia) oil. In: IFT Annual Meeting; 12-16 July 2004. Las Vegas Nevada USA.

  • 75. Matsuo AL Figueiredo CR Arruda DC Pereira FV Scutti JAB Massaoka MH Travassos LR Sartorelli P Lago JHG. α-Pinene isolated from Schinus terebinthifolius Raddi (Anacardiaceae) induces apoptosis and confers antimetastatic protection in a melanoma model. Biochem Biophys Res Commun 2011 ; 4 11 : 4 4 9 - 5 4 . d o i : 1 0 . 1 0 1 6 / j . bbrc.2011.06.176

  • 76. Constantinou A Mehta R Runyan C Rao K Vaughan A Moon R. Flavonoids as DNA topoisomerase antagonists and poisons: structure-activity relationships. J Nat Prod 1995;58:217-25. doi: 10.1021/np50116a009

  • 77. Lepley DM Li B Birt DF Pelling JC. The chemopreventive flavonoid apigenin induces G2/M arrest in keratinocytes. Carcinogenesis 1996;17:2367-75. PMID: 8968050

  • 78. Plaumann B Fritsche M Rimpler H Brandner G Hess RD.

  • Flavonoids activate wild-type p53. Oncogene 1996;13:1605-14. PMID: 8895505

  • 79. Agullo G Gamet-Payrastre L Manenti S Viala C Remesy C Chap H Payrastre B. Relationship between fl avonoid structure and inhibition of phosphatidylinositol 3-kinase: a comparison with tyrosine kinase and protein kinase C inhibition. Biochem Pharmacol 1997;53:1649-57. doi: 10.1016/S0006-2952(97)82453-7

  • 80. Chen ZP Schell JB Ho CT Chen KY. Green tea epigallocatechin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts. Cancer Lett 1998;129:173-9. doi: 10.1016/ S0304-3835(98)00108-6

  • 81. Kazi A Wang Z Kumar N Falsetti SC Chan TH Dou QP. Structure activity relationships of synthetic analogs of (−)- epigallocatechin-3-gallate as proteasome inhibitors. Anticancer Res 2004;24:943-54. PMID: 15161048

  • 82. Chen D Daniel KG Chen MS Kuhn DJ Landis-Piwowar KR Dou QP. Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells. Biochem Pharmacol 2005;69:1421-32. doi: 10.1016/j. bcp.2005.02.022

  • 83. Brusselmans K Vrolix R Verhoeven G Swinnen JV. Induction of cancer cell apoptosis by fl avonoids is associated with their ability to inhibit fatty acid synthase activity. J Biol Chem 2005;280:5636-45. doi: 10.1074/jbc.M408177200

  • 84. Turner SD Tinwell H Piegorsch W Schmezer P Ashby J. The male rat carcinogens limonene and sodium saccharin are not mutagenic to male Big Blue rats. Mutagenesis 2001;16:329-32. doi: doi: 10.1093/mutage/16.4.329

  • 85. Slamenova D Horvathova E Sramkova M Marsalkova L. DNA-protective effects of two components of essential plant oils carvacrol and thymol on mammalian cells cultured invitro. Neoplasma 2007;54:108-12. PMID: 17319782

  • 86. Gomes-Carneiro MR Viana ME Felzenszwalb I Paumgartten FJ. Evaluation of beta-myrcene alpha-terpinene and (+)- and (-)-alpha-pinene in the Salmonella/microsome assay. Food Chem Toxicol 2005;43:247-52. doi: 10.1016/j. fct.2004.09.011

  • 87. Horvath GY Kocsis B Botz L Nemeth J Hungarian LGy. Antibacterial activity of Thymus phenols by direct bioautography. Acta Biol Szegediensis 2002:46(3-4):145-6.

  • 88. Mademtzoglou D Akmoutsou P Kounatidis I Franzios G Drosopoulou E Vokou D Mavragani-Tsipidou P. Applying the Drosophila wing spot test to assess the genotoxic impact of 10 essential oil constituents used as fl avouring agents or cosmetic ingredients. Flavour Frag J 2011;26:447-51. doi: 10.1002/ffj.2081

  • 89. National Toxicology Program. NTP toxicology and carcinogenesis studies of d-carvone (CAS No. 2244-16-8) in B6C3F1mice (gavage studies). Natl Toxicol Program Tech Rep 1990;381:1-113. PMID: 12692655

  • 90. Singh NP McCoy MT Tice RR. A simple technique for quantitation of low level of DNA damage in individual cells. Exp Cell Res 1998;17:184-91. doi: 10.1016/0014-4827(88)90265-0

  • 91. Ravizza R Gariboldi MB Molteni R Monti E. Linalool a plant-derived monoterpene alcohol reverses doxorubicin resistance in human breast adenocarcinoma cells. Oncol Rep 2008;20:625-30. PMID: 18695915

  • 92. Hari Babu L Perumal S Balasubramanian MP. Myrtenal a natural monoterpene down-regulates TNF-α expression and suppresses carcinogen-induced hepatocellular carcinoma in rats. Mol Cell Biochem 2012;369:183-93. doi: 10.1007/ s11010-012-1381-0

  • 93. Soares PR de Oliveira PL de Oliveira CM Kato L Guillo LA. In vitro antiproliferative effects of the indole alkaloid vallesiachotamine on human melanoma cells. Arch Pharm Res 2012;35:565-71. doi: 10.1007/s12272-012-0320-7

  • 94. Kim SH Park EJ Lee CR Chun JN Cho NH Kim IG Lee S Kim TW Park HH So I Jeon JH. Geraniol induces cooperative interaction of apoptosis and autophagy to elicit cell death in PC-3 prostate cancer cells. Int J Oncol 2012;40:1683-90. doi: 10.3892/ijo.2011.1318

  • 95. Wu CS Chen YJ Chen JJ Shieh JJ Huang CH Lin PS Chang GC Chang JT Lin CC. Terpinen-4-ol induces apoptosis in human nonsmall cell lung cancer in vitro and invivo. Evid Based Complement Alternat Med 2012;2012:818261. doi: 10.1155/2012/818261

  • 96. Mohamed AA El-Emary GA Ali HF. Infl uence of some citrus essential oils on cell viability glutathione-S-transferase and lipid peroxidation in Ehrlich ascites carcinoma cells. J Am Sci 2010;6:820-6.

  • 97. Ohgami Y Elstad CA Chung E Shirachi DY Quock RM Lai HC. Effect of hyperbaric oxygen on the anticancer effect of artemisinin on molt-4 human leukemia cells. Anticancer Res 2010;30:4467-70. PMID: 21115894

  • 98. Zhou D Papayannis I Mackenzie GG Alston N Ouyang N Huang L Nie T Wong CC Rigas B. The anticancer effect of phospho-tyrosol-indomethacin (MPI 621) a novel phospho-derivative of indomethacin: In vitro and in vivo studies. Carcinogenesis 2013;34:943-51. doi: 10.1093/carcin/ bgs394)

  • 99. Kwan HY Yang Z Fong WF Hu YM Yu ZL Hsiao WLW. The anticancer effect of oridonin is mediated by fatty acid synthase suppression in human colorectal cancer cells. J Gastroenterol 2013;48:182-92. doi: 10.1007/s00535-012-0612-1

  • 100. Cai Y Luo Q Sun M Corke H. Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci 2004;74:2157-84. doi: 10.1016/j.lfs.2003.09.047

  • 101. Mates JM Segura JA Alonso FJ Marquez J Natural antioxidants: therapeutic prospects for cancer and neurological diseases. Mini-Rev Med Chem 2009;9:1202-14. doi: 10.21 74/138955709789055180

  • 102. Singh A Jain A Sarma B K Jha A Singh HB. Natural antioxidants and their role in cancer prevention. In: Shankar S Srivastava RK editors. Nutrition diet and cancer. Berlin: Springer; 2012. p. 563-83.

  • 103. Bourgou S Pichette A Lavoie S Marzouk B Legault J. Terpenoids isolated from Tunisian Nigella sativa L. essential oil with antioxidant activity and the ability to inhibit nitric oxide production. Flavour Frag J 2012;27:69-74. doi: 10.1002/ffj.2085

  • 104. Ruberto G Baratta MT. Anticancer antioxidant and antimicrobial activities of the essential oil of Lycopus lucidus Turcz. var. hirtus Regel. Food Chem 2000;69:167-74. doi: 10.1016/j.foodchem.2010.12.027

  • 105. Kim HJ Chen F Wu C Wang X Chung HY Jin Z. Evaluation of antioxidant activity of Australian tea tree (Melaleucaalternifolia) oil and its components. J Agric Food Chem 2004;52:2849-54. doi: 10.1021/jf035377d

  • 106. Lima CF Carvalho F Fernandes E Bastos ML Santos- Gomes PC Fernandes-Ferreira M Pereira-Wilson C. Evaluation of toxic/protective effects of the essential oil of Salvia officinalis on freshlyisolated rat hepatocytes. Toxicol In Vitro 2004;18:457-65. doi: 10.1016/j.tiv.2004.01.001

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