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Volume 68, Issue 4


A comparative study of cytotoxic, membrane and DNA damaging effects of Origanum majorana’s essential oil and its oxygenated monoterpene component linalool on parental and epirubicin-resistant H1299 cells

Ayse Erdogan / Aysun Ozkan
Published Online: 2013-06-13 | DOI: https://doi.org/10.2478/s11756-013-0196-0


In this study, cytotoxic, membrane and DNA damaging effects of the essential oil from Origanum majorana and its oxygenated monoterpene component linalool were tested on parental and epirubicin-resistant (drug-resistant) human lung cancer cell lines (H1299). Essential oil’s and linalool’s cytotoxicities were examined and parental cells were found more sensitive to the essential oil’s and linalool’s cytotoxicities than drug-resistant cells. O. majorana essential oil had more effective membrane damaging effect than linalool on parental cells, while in drug-resistant H1299 cells, linalool had more effective membrane damaging effect than the essential oil. O. majorana essential oil possessed more effective DNA damaging effect than linalool on both parental and drug-resistant cells. The conclusions from this study suggest that O. majorana essential oil and linalool exhibit cytotoxic, membrane and DNA damaging effects. They thus need further investigation as potential therapeutic agents for human lung cancer.

Keywords: Origanum majorana; essential oil; linalool; DNA damage; membrane damage; parental and epirubicin-resistant H1299 cell line

  • [1] Abdel-Massih R.M., Fares R., Bazzi S., El Chami N. & Baydoun E. 2010. The apoptotic and anti-proliferative activity of Origanum majorana extracts on human leukemic cell line. Leukemia Res. 34: 1052–1056. http://dx.doi.org/10.1016/j.leukres.2009.09.018CrossrefGoogle Scholar

  • [2] Al-Howiriny T., Alsheikh A., Alqasoumi S., Al-Yahya M., ElTahir K. & Rafatullah S. 2009. Protective effect of Origanum majorana L.’ Marjoram’ on various models of gastric mucosal injury in rats. Am. J. Chinese Med. 37: 531–545. http://dx.doi.org/10.1142/S0192415X0900703XCrossrefGoogle Scholar

  • [3] Armstrong J.S. 2006. Mitochondrial membrane permeabilization: the sine qua non for cell death. BioEssays 28: 253–260. http://dx.doi.org/10.1002/bies.20370CrossrefGoogle Scholar

  • [4] Bakkali F., Averbeck S., Averbeck D. & Idaomar M. 2008. Biological effects of essential oils — a review. Food Chem. Toxicol. 46: 446–475. http://dx.doi.org/10.1016/j.fct.2007.09.106CrossrefGoogle Scholar

  • [5] Bard M., Albrecht M. R., Gupta N., Guynn C. J. & Stillwell W. 1998. Geraniol interferes with membrane functions in strains of Candida and Saccharomyces. Lipids 23: 534–538. http://dx.doi.org/10.1007/BF02535593CrossrefGoogle Scholar

  • [6] Beckman K.B. & Ames B.N. 1998. The free radical theory of aging matures. Physiol. Rev. 71: 547–581. Google Scholar

  • [7] Bickers D., Calow P., Greim H., Hanifin J.M., Rogers A.E., Saurat J.H., Sipes I.G., Smith R.L. & Tagami H.A. 2003. Toxicological and dermatological assessment of linalool and related esters when used as fragrance ingredients. Food Chem. Toxicol. 41: 919–942. http://dx.doi.org/10.1016/S0278-6915(03)00016-4CrossrefGoogle Scholar

  • [8] Bradford M.M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal. Biochem. 72: 248–254. http://dx.doi.org/10.1016/0003-2697(76)90527-3CrossrefGoogle Scholar

  • [9] Brehm-Stecher B.F. & Johnson E.A. 2003. Sensitization of Staphylococcus aureus and Escherichia coli to antibiotics by the sequiterpenoids, nerolidol, farnesol, bisabolol and apritone. Antimicrob. Agents Chemother. 47: 3357–3360. http://dx.doi.org/10.1128/AAC.47.10.3357-3360.2003CrossrefGoogle Scholar

  • [10] Buettner G.R. 1993. The pecking order of free radicals and antioxidants: lipid peroxidation, α-tocopherol and ascorbate. Arch. Biochem. Biophys. 300: 535–543. http://dx.doi.org/10.1006/abbi.1993.1074CrossrefGoogle Scholar

  • [11] Busatta C., Vidal R.S., Popiolski A.S., Mossi A.J., Dariva C., Rodrigues M.R.A, Corazza F.C., Corazza M.I., Oliveira J.V. & Cansian R.I. 2008. Application of Origanum majorana L. essential oil as an antimicrobial agent in sausage. Food Microbiol. 25: 207–211. http://dx.doi.org/10.1016/j.fm.2007.07.003CrossrefGoogle Scholar

  • [12] Butler P.J., Tsou T., Li J.Y., Usami S. & Chien S. 2002. Rate sensitivity of shear induced changes in the lateral diffusion of endothelial cell membrane lipids: a role for membrane perturbation in shear-induced MAPK activation. FASEB J. 16: 216–218. Google Scholar

  • [13] Cal K. 2006. Skin penetration of terpenes from essential oils and topical vehicles. Planta Med. 72: 311–316. http://dx.doi.org/10.1055/s-2005-916230CrossrefGoogle Scholar

  • [14] Daayf F. & Lattanzio V. 2008. Recent Advances in Polyphenol Research. Volume 1. Blackwell Publishing, Ltd. http://dx.doi.org/10.1002/9781444302400CrossrefGoogle Scholar

  • [15] Dobbs N.A., Twelwes C.J., Rizzi P., Warvick J.D., Metivier E.M., Williams R. & Johnson P.J. 1994. Epirubicin in hepatocellular carcinoma: pharmacokinetics and clinical activity. Cancer Chemother. Pharmacol. 34: 405–410. http://dx.doi.org/10.1007/BF00685565CrossrefGoogle Scholar

  • [16] El-Ashmawy I.M., El-Nahas A.F. & Salama O.M. 2005. Protective effect of volatile oil, alcoholic and aqueous extracts of Origanum majorana on lead acetate toxicity in mice. Basic Clin. Pharmacol. Toxicol. 97: 238–243. http://dx.doi.org/10.1111/j.1742-7843.2005.pto_136.xCrossrefGoogle Scholar

  • [17] Erdogan A. & Ozkan A. 2013. Effects of Thymus revolutus Célak essential oil and its two major components on Hep G2 cells membrane. Biologia 68: 105–111. http://dx.doi.org/10.2478/s11756-012-0144-4Google Scholar

  • [18] Esen G., Azaz A.D., Kurkcuoglu M., Baser K.H.C. & Tinmaz A. 2007. Essential oil and antimicrobial activity of wild and cultivated Origanum vulgare L. subsp. Hirtum (Link) letswaart from the Marmara region, Turkey. Flavour Frag. J. 22: 371–376. http://dx.doi.org/10.1002/ffj.1808CrossrefGoogle Scholar

  • [19] Franzios G., Mirotsou M., Hatziapostolou E., Kral J., Scouras Z.G. & Mavragani-Tsipidou P. 1997. Insecticidal and genotoxic activities of mint essential oils. J. Agric. Food Chem. 45: 2690–2694. http://dx.doi.org/10.1021/jf960685fCrossrefGoogle Scholar

  • [20] Fridovich I. 1978. The biology of oxygen radicals. Science 201: 875–880. http://dx.doi.org/10.1126/science.210504CrossrefGoogle Scholar

  • [21] Gloeckner H., Jonuleit T. & Lemke H.D. 2001. Monitoring of cell viability and cell growth in a hollow-fiber bioreactor by use of the dye Alamar Blue (TM). J. Immunol. Methods 252: 131–138. http://dx.doi.org/10.1016/S0022-1759(01)00347-7CrossrefGoogle Scholar

  • [22] Goulart H.R., Kimura E.A., Peres V.J., Couto A.S., Aquino Duarte F.A. & Katzin A.M. 2004. Terpenes arrest parasite development and inhibit biosynthesis of terpenoids in Plasmodium falciparum. Antimicrob. Agents Chemother. 48: 2502–2509. http://dx.doi.org/10.1128/AAC.48.7.2502-2509.2004CrossrefGoogle Scholar

  • [23] Halliwell B. 1999. Oxygen and nitrogen are procarcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutat. Res. 44: 37–52. CrossrefGoogle Scholar

  • [24] Hoet S., Stevigny C., Herent M.F. & Quetin-Leclercq J. 2006. Antitrypanosomal compounds from leaf essential oil of Strychnos spinosa. Planta Med. 72: 480–482. http://dx.doi.org/10.1055/s-2005-916255CrossrefGoogle Scholar

  • [25] Hong L., Piao Y., Han Y., Wang J., Zhang X., Du Y., Cao S., Qiao T., Chen Z. & Fan D. 2005. Zinc ribbon domain containing 1 (ZNRD1) mediates multidrug resistance of leukemia cells through regulation of P-glycoprotein and Bcl-2. Mol. Cancer Ther. 4: 1936–1942. http://dx.doi.org/10.1158/1535-7163.MCT-05-0182CrossrefGoogle Scholar

  • [26] Hussain A.I., Anwar F., Rasheed S., Nigam P.S., Janneh O. & Sarker S.D. 2011. Composition, antioxidant and chemotherapeutic properties of the essential oils from two Origanum species growing in Pakistan. Rev. Bras. Farmacogn. 21: 943–952. http://dx.doi.org/10.1590/S0102-695X2011005000165CrossrefGoogle Scholar

  • [27] Jansson O., Motlagh P.B., Persson M., Henrikson R. & Grankvist K. 1999. Increase in doxorubicin cytotoxicity by carvedilol inhibition of P-glycoprotein activity. Biochemical Pharmacol. 58: 1801–1806 http://dx.doi.org/10.1016/S0006-2952(99)00262-2CrossrefGoogle Scholar

  • [28] Kikuchi A., Takeda A., Onodera H., Kimpara T., Hisanaga K., Sato N., Nunomura A., Castellani R.J., Perry G., Smith M.A. & Itoyama Y. 2002. Systemic increase of oxidative nucleic acid damage in Parkinson’s disease and multiple system atrophy. Neurobiol. Dis. 9: 244–248. http://dx.doi.org/10.1006/nbdi.2002.0466CrossrefGoogle Scholar

  • [29] Koparal A.T. & Zeytinoglu M. 2003. Effects of carvacrol on a human nonsmall cell lung cancer (NSCLC) cell line, A549. Cytotechnology 43: 149–154. http://dx.doi.org/10.1023/B:CYTO.0000039917.60348.45CrossrefGoogle Scholar

  • [30] Lin L.T., Liu L.T., Chiang L.C. & Lin C.C. 2002. In vitro antihepatoma activity of fifteen natural medicines from Canada. Phytother. Res. 16: 440–444. http://dx.doi.org/10.1002/ptr.937CrossrefGoogle Scholar

  • [31] Lorenzi V., Muselli A., Bernardini A., Berti L., Pagčs J. M., Amaral, L. & Bolla J. M. 2009. Geraniol restores antibiotic activities against multidrug-resistant isolates from Gram-negative species. Antimicrob. Agents Chemother. 53: 2209–2211. http://dx.doi.org/10.1128/AAC.00919-08CrossrefGoogle Scholar

  • [32] Mak I.T., Misra H.P. & Weglicki W.B. 1983. Temporal relationship of free radical induced lipid peroxidation and loss of latent enzyme activity in highly enriched hepatic lysosomes. J. Biol. Chem. 258: 13733–13737. Google Scholar

  • [33] Mo H. & Elson C. C. 2004. Studies on the isoprenoid-mediated inhibition of mevalonate synthesis applied to cancer chemotherapy and chemoprevention. Exp. Biol. Med. 229: 567–585. Google Scholar

  • [34] Novgorodov S.A. & Gudz T.I. 1996. Permeability transition pore of the inner mitochondrial membrane can operate in two open states with different selectivities. J. Bioenerg. Biomembr. 28: 139–146. http://dx.doi.org/10.1007/BF02110644CrossrefGoogle Scholar

  • [35] Ota Y., Hamada A., Nakano M. & Saito H. 2003. Evaluation of percutaneous absorption of midazolan by terpenes. Drugs Metabol. Pharmacokin. 18: 261–266. http://dx.doi.org/10.2133/dmpk.18.261CrossrefGoogle Scholar

  • [36] Ozkan A. 2007. Lymphokine-activated killer cell susceptibility in epirubicin resistant and parental human non-small cell lung cancer (NSCLC). Biologia 62: 232–237. http://dx.doi.org/10.2478/s11756-007-0040-5CrossrefGoogle Scholar

  • [37] Ozkan A. & Erdogan A. 2011. A comparative evaluation of antioxidant and anticancer activity of essential oil from Origanum onites (Lamiaceae) and its two major phenolic components. Turk. J. Biol. 35: 735–742. Google Scholar

  • [38] Ozkan A. & Erdogan A. 2012a. A comparative study of the antioxidant/prooxidant effects of carvacrol and thymol at various concentrations on membrane and DNA of parental and drug resistant H1299 cells. Nat. Prod. Commun. 7: 1557–1560. Google Scholar

  • [39] Ozkan A. & Erdogan A. 2012b. Membrane and DNA damaging/protective effects of eugenol, eucalyptol, terpinen-4-ol and camphor at various concentrations on parental and drug resistant H1299 cells. Turk. J. Biol. DOI: 10.3906/biy-1208-4. CrossrefGoogle Scholar

  • [40] Ozkan A. & Erdogan A. 2012c. Antioxidant and anticancer activity of fresh corm extract from Romulea tempskyana (Iridaceae). Nat. Prod. Res. 26: 2126–2128. Google Scholar

  • [41] Ozkan A., Erdogan A., Sokmen M., Tugrulay S. & Unal O. 2010. Antitumoral and antioxidant effect of essential oils and in vitro antioxidant properties of essential oils and aqueous extracts from Salvia pisidica. Biologia 65: 990–996. http://dx.doi.org/10.2478/s11756-010-0108-5CrossrefGoogle Scholar

  • [42] Ramadan G., El-Beih N.M. & Zahra M.M. 2012. Egyptian sweet marjoram leaves protect against genotoxicity, immunosuppression and other complications induced by cyclophosphamide in albino rats. Brit. J. Nutr. 108: 1059–1068. http://dx.doi.org/10.1017/S0007114511006210CrossrefGoogle Scholar

  • [43] Ramage G., Saville S.P., Wicks B.L. & Lopez-Ribot J.L. 2002. Inhibition of Candida albicans biofilm formation by farnesol, a quorum-sensing molecule. Appl. Environ. Microbiol. 68: 5459–5463. http://dx.doi.org/10.1128/AEM.68.11.5459-5463.2002CrossrefGoogle Scholar

  • [44] Ren W., Zhenhua Q., Hongwei W., Zhu L. & Zhang L. 2003. Flavonoids: promising anticancer agents. Med. Res. Rev. 23: 519–534. http://dx.doi.org/10.1002/med.10033CrossrefGoogle Scholar

  • [45] Richter C. & Schlegel J. 1993. Mitochondrial calcium release induced by prooxidants. Toxicol. Lett. 67: 119–127. http://dx.doi.org/10.1016/0378-4274(93)90050-8CrossrefGoogle Scholar

  • [46] Rihova B., Strohalm J. & Kobackova K. 2002. Acquired and specific immunological mechanisms co-responsible for efficacy of polymer-bound drugs. J. Control. Release 78: 97–114. http://dx.doi.org/10.1016/S0168-3659(01)00489-8CrossrefGoogle Scholar

  • [47] Santana-Rios G., Orner G.A., Amantana A., Provost C., Wu S.Y. & Dashwood R.H. 2001. Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay. Mutat. Res. 495: 61–74. http://dx.doi.org/10.1016/S1383-5718(01)00200-5CrossrefGoogle Scholar

  • [48] Sari M., Biondi D.M., Kaabeche M., Mandalari G., D’Arrigo M., Bisignano G., Saija A., Daquino C. & Ruberto G. 2006. Chemical composition, antimicrobial and antioxidant activities of the essential oil of several populations of Algerian Origanum glandulosum Desf. Flav. Fragr. J. 21: 890–898. http://dx.doi.org/10.1002/ffj.1738CrossrefGoogle Scholar

  • [49] Toyokuni S., Tanaka T., Hattori Y., Nishiyama Y., Yoshida A., Uchida K., Hiai H., Oci H. & Osawa T. 1997. Quantitative immunohistochemical determination of 8-hydroxy-2′-deoxyguanosine by a monoclonal antibody N45. 1: its application to ferric nitriloacetate-induced renal carcinogenesis model. Lab. Invest. 76: 365–374. Google Scholar

  • [50] Trombetta D., Castelli F., Sarpietro M. G., Venuti V., Cristani M., Daniele C., Saija A., Mazzanti G. & Bisignano G. 2005. Mechanisms of antibacterial activity of three monoterpenes. Antimicrob. Agents Chemother. 49: 2474–2478. http://dx.doi.org/10.1128/AAC.49.6.2474-2478.2005CrossrefGoogle Scholar

  • [51] Valavanidis A., Vlachogianni T. & Fiotakis C. 2009. 8-hydroxy-2′-deoxyguanosine (8-OHdG): a critical biomarker of oxidative stress and carcinogenesis. J. Environ. Sci. Health C27: 120–139. Google Scholar

  • [52] Vercesi A.E., Kowaltowski A.J., Grijalba M.T., Meinicke A.R. & Castilho R.F. 1997. The role of reactive oxygen species in mitochondrial permeability transition. Biosci. Rep. 17: 43–52. http://dx.doi.org/10.1023/A:1027335217774CrossrefGoogle Scholar

  • [53] Wasowicz W., Neve J. & Peretz A. 1993. Optimized steps in fluorometric determination of thiobarbitiric acid-reactive substances in serum; importance of extraction pH and influence of sample preservation and storage. Clin. Chem. 39: 2522–2526. Google Scholar

  • [54] Yoon H.S., Moon S.C., Kim N.D., Park B.S., Jeong M.H. & Yoo Y.H. 2000. Genistein induces apoptosis of RPE-J cells by opening mitochondrial PTP. Biochem. Biophys. Res. Commun. 276: 151–156. http://dx.doi.org/10.1006/bbrc.2000.3445CrossrefGoogle Scholar

About the article

Published Online: 2013-06-13

Published in Print: 2013-08-01

Citation Information: Biologia, Volume 68, Issue 4, Pages 754–761, ISSN (Online) 1336-9563, ISSN (Print) 0006-3088, DOI: https://doi.org/10.2478/s11756-013-0196-0.

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