×
Home Current Archive Editorial board
News Contact
Research Article

Novel insights to the anti-proliferative activity of rosemary (Rosmarinus officinalis L.) co-treatment

By
Jasminka Mrđanović ,
Jasminka Mrđanović

Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Višnja Bogdanović ,
Višnja Bogdanović

University of Novi Sad, Novi Sad, Serbia

Biljana Kiprovski ,
Biljana Kiprovski
Contact Biljana Kiprovski

Institute of Field and Vegetable Crops, Novi Sad, Serbia

Đorđe Malenčić ,
Đorđe Malenčić

Department of Field and Vegetable Crops, Faculty of Agriculture, University of Novi Sad, Novi Sad, Serbia

Maja Mikulič-Petkovšek ,
Maja Mikulič-Petkovšek

Department of Agronomy, Biotechnical faculty, University of Ljubljana, Ljubljana, Slovenia

Ivan Milovanović ,
Ivan Milovanović

Institute of Food Technology, Novi Sad, Serbia

Aleksandra Mišan
Aleksandra Mišan

Institute of Food Technology, Novi Sad, Serbia

Abstract

The aim of this study was to characterize volatile and non-volatile compounds of rosemary from the North Adriatic region and to determine its antiproliferative activity, alone or in combination with radiomimetic bleomycin (BLM) on three malignant and one non-transformed human cell line. Chemical analysis of the volatile compounds revealed the presence of monoterpenes (93.8%), in which 1.8-cineol (32.9%) and camphor (15.5%) were the dominant compounds. Also, obtained results showed that the major polyphenolic constituents in rosemary extract were phenolic acids (rosmarinic acid and its derivatives up to 69.2 mg 100 g-1), as well as flavones and flavonols in the following order: luteolin>isorhamnetin>quercetin>kaempferol>apigenin. Cell growth test showed that rosemary extract alone exerted moderate antiproliferative activity, as well as a synergistic antiproliferative effect with bleomycin (EC50 344.3-461.5 µg mL-1 and 58.6-292 µg mL-1, respectively). The anti-tumor effect of rosemary extract in combination with BLM was much stronger, compared to BLM itself on the breast cancer cells. Through their proposed sensitizing effect, rosemary extracts, in combination with the standard chemotherapeutics, could be used for the investigations of possible therapeutic modalities.


 

References

[{"id":3532,"citationNumber":"1.","type":"book","title":"Identification of essential oil components by gas chromatography\/mass spectrometry","DOI":null,"author":[{"given":"R.P.","family":"Adams"}],"issued":{"date-parts":["2007"]},"container-title":null,"volume":"456","issue":null,"page":null}]

[{"id":3533,"citationNumber":"2.","type":"article-journal","title":"DNA damage by benzo (a) pyrene in human cells is increased by cigarette smoke and decreased by a filter containing rosemary extract, which lowers free radicals","DOI":null,"author":[{"given":"K.","family":"Alexandrov"},{"given":"M.","family":"Rojas"},{"given":"C.","family":"Rolando"}],"issued":{"date-parts":["2006"]},"container-title":"Cancer Res","volume":"66","issue":"24","page":"1938\u20131945"}]

[{"id":3534,"citationNumber":"3.","type":"article-journal","title":"Essential oils used in aromatherapy: A systemic review","DOI":null,"author":[{"given":"B.","family":"Ali"},{"given":"N.A.","family":"Al-Wabel"},{"given":"S.","family":"Shams"},{"given":"A.","family":"Ahamad"},{"given":"S.A.","family":"Khan"},{"given":"F.","family":"Anwar"}],"issued":{"date-parts":["2015"]},"container-title":"Asian Pac. J. Trop. Biomed","volume":"5","issue":"8","page":"601\u2013611"}]

[{"id":3535,"citationNumber":"4.","type":"article-journal","title":"Extraction of rosemary essential oil by steam distillation and hydrodistillation","DOI":null,"author":[{"given":"C.","family":"Boutekedjiret"},{"given":"F.","family":"Bentahar"},{"given":"R.","family":"Belabbes"},{"given":"J.M.","family":"Bessiere"}],"issued":{"date-parts":["2003"]},"container-title":"Flavour Fragr. J","volume":"18","issue":"6","page":"481\u2013484"}]

[{"id":3536,"citationNumber":"5.","type":"article-journal","title":"Bioactivity of Meeker and Willamette raspberry (Rubus idaeus L.) pomace extracts","DOI":null,"author":[{"given":"D.D.","family":"\u010cetojevi\u0107-Simin"},{"given":"A.S.","family":"Veli\u0107anski"},{"given":"D.D.","family":"Cvetkovi\u0107"},{"given":"S.L.","family":"Markov"},{"given":"G.S.","family":"\u0106etkovi\u0107"},{"given":"V.T.","family":"\u0160aponjac"},{"given":"J.J.","family":"Vuli\u0107"},{"given":"J.M.","family":"\u010canadanovi\u0107-Brunet"},{"given":"S.M.","family":"Djilas"}],"issued":{"date-parts":["2015"]},"container-title":"Food Chem","volume":"166","issue":null,"page":"407\u2013413"}]

[{"id":3537,"citationNumber":"6.","type":"article-journal","title":"Anti-proliferative and antioxidant properties of rosemary Rosmarinus officinalis","DOI":null,"author":[{"given":"S.","family":"Cheung"},{"given":"J.","family":"Tai"}],"issued":{"date-parts":["2007"]},"container-title":"Oncol. Rep","volume":"17","issue":"6","page":"1525\u20131531"}]

[{"id":3538,"citationNumber":"7.","type":"article-journal","title":"European Pharmacopoeia Commission, and the European Directorate for the Quality of Medicines & HealthCare","DOI":null,"author":[{"given":"European","family":"Pharmacopoeia"}],"issued":{"date-parts":["2013"]},"container-title":null,"volume":"VIII) Vol. 1","issue":null,"page":null}]

[{"id":3539,"citationNumber":"8.","type":"article-journal","title":"Antitumor effect of 5-fluorouracil is enhanced by rosemary extract in both drug sensitive and resistant colon cancer cells","DOI":null,"author":[{"given":"M.","family":"Gonz\u00e1lez-Vallinas"},{"given":"S.","family":"Molina"},{"given":"G.","family":"Vicente"},{"given":"A.","family":"Cueva"},{"given":"T.","family":"Vargas"},{"given":"S.","family":"Santoyo"},{"given":"M.R.","family":"Garcia-Risco"},{"given":"T.","family":"Fornari"},{"given":"G.","family":"Reglero"},{"given":"A.R.","family":"Molina"}],"issued":{"date-parts":["2013"]},"container-title":"Pharmacol. Res","volume":"72","issue":null,"page":"61\u201368"}]

[{"id":3540,"citationNumber":"9.","type":"article-journal","title":"Modulation of estrogen and epidermal growth factor receptors by rosemary extract in breast cancer cells","DOI":null,"author":[{"given":"M.","family":"Gonz\u00e1lez\u2010Vallinas"},{"given":"S.","family":"Molina"},{"given":"G.","family":"Vicente"},{"given":"R.","family":"S\u00e1nchez\u2010Mart\u00ednez"},{"given":"T.","family":"Vargas"},{"given":"M.R.","family":"Garc\u00eda\u2010Risco"},{"given":"T.","family":"Fornari"},{"given":"G.","family":"Reglero"},{"given":"A.","family":"Molina"}],"issued":{"date-parts":["2014"]},"container-title":"Electrophoresis","volume":"35","issue":"11","page":"1719\u20131727"}]

[{"id":3541,"citationNumber":"10.","type":"article-journal","title":"Cuminum cyminum fruits as source of luteolin-7-O-glucoside, potent cytotoxic flavonoid against breast cancer cell lines","DOI":null,"author":[{"given":"S.","family":"Goodarzi"},{"given":"M.J.","family":"Tabatabaei"},{"given":"R.","family":"Mohammad Jafari"},{"given":"F.","family":"Shemirani"},{"given":"S.","family":"Tavakoli"},{"given":"M.","family":"Mofasseri"},{"given":"Z.","family":"Tofighi"}],"issued":{"date-parts":["2018"]},"container-title":"Nat. Prod","volume":"Res.18","issue":null,"page":"1\u20135"}]

[{"id":3542,"citationNumber":"11.","type":"article-journal","title":"Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines","DOI":null,"author":[{"given":"A.Q.","family":"Haddad"},{"given":"V.","family":"Venkateswaran"},{"given":"L.","family":"Viswanathan"},{"given":"S.J.","family":"Teahan"},{"given":"N.E.","family":"Fleshner"},{"given":"L.H.","family":"Klotz"}],"issued":{"date-parts":["2006"]},"container-title":"Prostate Cancer Prostatic Dis","volume":"9","issue":"1","page":"68"}]

[{"id":3543,"citationNumber":"12.","type":"article-journal","title":"Redox-modulating and\/or antioxidant properties of niroxides\u2013a potential reason for decreasing side-effects of cancer therapy","DOI":null,"author":[{"given":"D.","family":"Ivanova"},{"given":"E.","family":"Georgieva"},{"given":"D.","family":"Lazarova"},{"given":"V.","family":"Gadjeva"},{"given":"R.","family":"Bakalova"},{"given":"Z.","family":"Zhelev"}],"issued":{"date-parts":["2014"]},"container-title":"Trakia J. Sci","volume":"12","issue":"3","page":"325"}]

[{"id":3544,"citationNumber":"13.","type":"article-journal","title":"Chemical composition of hydrodistillation essential oil of rosemary in different origins in Iran and comparison with other countries","DOI":null,"author":[{"given":"R.","family":"Jamshidi"},{"given":"Z.","family":"Afzali"},{"given":"D.","family":"Afzali"}],"issued":{"date-parts":["2009"]},"container-title":"Am Eurasian J Agric Environ Sci","volume":"5","issue":"1","page":"78\u201381"}]

[{"id":3545,"citationNumber":"14.","type":"article-journal","title":"Comparative antibacterial activity of five Lamiaceae essential oils from Algeria","DOI":null,"author":[{"given":"Z.","family":"Kabouche"},{"given":"N.","family":"Boutaghane"},{"given":"S.","family":"Laggoune"},{"given":"A.","family":"Kabouche"},{"given":"Z.","family":"Ait-Kaki"},{"given":"K.","family":"Benlabed"}],"issued":{"date-parts":["2005"]},"container-title":"Int. J. Aromather","volume":"15","issue":"3","page":"129\u201333"}]

[{"id":3546,"citationNumber":"15.","type":"article-journal","title":"Synergistic antiproliferative and anticholesterogenic effects of linalool, 1,8-cineole, and simvastatin on human cell lines","DOI":null,"author":[{"given":"B.R.","family":"Kladniew"},{"given":"M.","family":"Polo"},{"given":"S.M.","family":"Villegas"},{"given":"M.","family":"Galle"},{"given":"R.","family":"Crespo"},{"given":"M.G.","family":"Bravo"}],"issued":{"date-parts":["2014"]},"container-title":"Chem. Biol. Interact","volume":"214","issue":null,"page":"57\u201368"}]

[{"id":3547,"citationNumber":"16.","type":"article-journal","title":"Functional properties of spice extracts obtained via supercritical fluid extraction","DOI":null,"author":[{"given":"J.E.","family":"Carvalho"},{"given":"M.O.","family":"Marques"},{"given":"M.A.","family":"Meireles"}],"issued":{"date-parts":["2003"]},"container-title":"J. Agric. Food Chem","volume":"51","issue":"9","page":"2520\u20132525"}]

[{"id":3548,"citationNumber":"17.","type":"article-journal","title":"Synergistic interactions between anticancer chemotherapeutics and phenolic compounds and anticancer synergy between polyphenols","DOI":null,"author":[{"given":"U.","family":"Lewandowska"},{"given":"S.","family":"Gorlach"},{"given":"K.","family":"Owczarek"},{"given":"E.","family":"Hrabec"},{"given":"K.","family":"Szewczyk"}],"issued":{"date-parts":["2014"]},"container-title":"Adv. Hyg. Exp. Med","volume":"68","issue":null,"page":null}]

[{"id":3549,"citationNumber":"18.","type":"article-journal","title":"Inhibitory effects of rosmarinic acid on the proliferation of cultured murine mesangial cells","DOI":null,"author":[{"given":"T.","family":"Makino"},{"given":"T.","family":"Ono"},{"given":"E.","family":"Muso"},{"given":"H.","family":"Yoshida"},{"given":"G.","family":"Honda"},{"given":"S.","family":"Sasayama"}],"issued":{"date-parts":["2000"]},"container-title":"Nephrol. Dial. Transplant","volume":"15","issue":"8","page":"1140\u20131145"}]

[{"id":3550,"citationNumber":"19.","type":"article-journal","title":"Alteration of the content of primary and secondary metabolites in strawberry fruit by Colletotrichum nymphaeae infection","DOI":null,"author":[{"given":"M.","family":"Mikulic-Petkovsek"},{"given":"V.","family":"Schmitzer"},{"given":"A.","family":"Slatnar"},{"given":"N.","family":"Weber"},{"given":"R.","family":"Veberic"},{"given":"F.","family":"Stampar"},{"given":"A.","family":"Munda"},{"given":"D.","family":"Koron"}],"issued":{"date-parts":["2013"]},"container-title":"J. Agri. Food Chem","volume":"61","issue":"25","page":"5987\u20135995"}]

[{"id":3551,"citationNumber":"20.","type":"article-journal","title":"The formation of phenolic diterpenes in Rosmarinus officinalis L. under Mediterranean climate","DOI":null,"author":[{"given":"S.","family":"Munn\u00e9-Bosch"},{"given":"L.","family":"Alegre"},{"given":"K.","family":"Schwarz"}],"issued":{"date-parts":["2000"]},"container-title":"Eur. Food Res. Technol","volume":"210","issue":"4","page":"263\u2013267"}]

[{"id":3552,"citationNumber":"21.","type":"article-journal","title":"Terpinolene, a component of herbal sage, downregulates AKT1 expression in K562 cells","DOI":null,"author":[{"given":"N.","family":"Okumura"},{"given":"H.","family":"Yoshida"},{"given":"Y.","family":"Nishimura"},{"given":"Y.","family":"Kitagishi"},{"given":"S.","family":"Matsuda"}],"issued":{"date-parts":["2012"]},"container-title":"Oncology Lett","volume":"3","issue":"2","page":"321\u2013324"}]

[{"id":3553,"citationNumber":"22.","type":"article-journal","title":"Determination of active components in rosemary by capillary electrophoresis with electrochemical detection","DOI":null,"author":[{"given":"Y.","family":"Peng"},{"given":"J.","family":"Yuan"},{"given":"F.","family":"Liu"},{"given":"J.","family":"Ye"}],"issued":{"date-parts":["2005"]},"container-title":"J. Pharmaceut. Biomed","volume":"39","issue":"3-4","page":"431\u2013437"}]

[{"id":3554,"citationNumber":"23.","type":"article-journal","title":"Rosemary (Rosmarinus officinalis) extract modulates CHOP\/GADD153 to promote androgen receptor degradation and decreases xenograft tumor growth","DOI":null,"author":[{"given":"S.M.","family":"Petiwala"},{"given":"S.","family":"Berhe"},{"given":"G.","family":"Li"},{"given":"A.G.","family":"Puthenveetil"},{"given":"O.","family":"Rahman"},{"given":"L.","family":"Nonn"},{"given":"J.J.","family":"Johnson"}],"issued":{"date-parts":["2014"]},"container-title":"PloS one","volume":"9","issue":"3","page":"89772"}]

[{"id":3555,"citationNumber":"24.","type":"article-journal","title":"Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity","DOI":null,"author":[{"given":"S.M.","family":"Petiwala"},{"given":"J.J.","family":"Johnson"}],"issued":{"date-parts":["2015"]},"container-title":"Cancer Lett","volume":"367","issue":"2","page":"93\u2013102"}]

[{"id":3556,"citationNumber":"25.","type":"article-journal","title":"DNA damage and mutagenesis by radiomimetic DNA-cleaving agents: bleomycin, neocarzinostatin and other enediynes","DOI":null,"author":[{"given":"L.F.","family":"Povirk"}],"issued":{"date-parts":["1996"]},"container-title":"Mutat. Res","volume":"355","issue":"1-2","page":"71\u201389"}]

[{"id":3557,"citationNumber":"26.","type":"article-journal","title":"Inhibitory effect of caffeic acid on cancer cell proliferation by oxidative mechanism in human HT-1080 fibrosarcoma cell line","DOI":null,"author":[{"given":"N.R.","family":"Prasad"},{"given":"A.","family":"Karthikeyan"},{"given":"S.","family":"Karthikeyan"},{"given":"B.V.","family":"Reddy"}],"issued":{"date-parts":["2011"]},"container-title":"Mol. Cell. Biochem","volume":"349","issue":"1-2","page":"11\u201319"}]

[{"id":3558,"citationNumber":"27.","type":"article-journal","title":"Flavonoids: promising anticancer agents","DOI":null,"author":[{"given":"W.","family":"Ren"},{"given":"Z.","family":"Qiao"},{"given":"H.","family":"Wang"},{"given":"L.","family":"Zhu"},{"given":"L.","family":"Zhang"}],"issued":{"date-parts":["2003"]},"container-title":"Med. Res. Rev","volume":"23","issue":"4","page":"519\u201334"}]

[{"id":3559,"citationNumber":"28.","type":"article-journal","title":"Comparison of in vitro anticancer-drug-screening data generated with a tetrazolium assay versus a protein assay against a diverse panel of human tumor cell lines","DOI":null,"author":[{"given":"L.V.","family":"Rubinstein"},{"given":"R.H.","family":"Shoemaker"},{"given":"K.D.","family":"Paull"},{"given":"R.M.","family":"Simon"},{"given":"S.","family":"Tosini"},{"given":"P.","family":"Skehan"},{"given":"D.A.","family":"Scudiero"},{"given":"A.","family":"Monks"},{"given":"M.R.","family":"Boyd"}],"issued":{"date-parts":["1990"]},"container-title":"J. Natl. Cancer Inst","volume":"82","issue":"13","page":"1113\u20131117"}]

[{"id":3560,"citationNumber":"29.","type":"article-journal","title":"Effect of rosmarinus officinalis in modulating 7, 12\u2010dimethylbenz (a) anthracene induced skin tumorigenesis in mice","DOI":null,"author":[{"given":"G.","family":"Sancheti"},{"given":"P.K.","family":"Goyal"}],"issued":{"date-parts":["2006"]},"container-title":"Phytother. Res","volume":"20","issue":"11","page":"981\u2013986"}]

[{"id":3561,"citationNumber":"30.","type":"book","title":"The healing intelligence of essential oils: the science of advanced aromatherapy","DOI":null,"author":[{"given":"K.","family":"Schnaubelt"}],"issued":{"date-parts":["2011"]},"container-title":null,"volume":null,"issue":null,"page":null}]

[{"id":3562,"citationNumber":"31.","type":"article-journal","title":"Preventive and protective properties of rosemary (Rosmarinus officinalis L.) in obesity and diabetes mellitus of metabolic disorders: a brief review","DOI":null,"author":[{"given":"R.","family":"Sedighi"},{"given":"Y.","family":"Zhao"},{"given":"A.","family":"Yerke"},{"given":"S.","family":"Sang"}],"issued":{"date-parts":["2015"]},"container-title":"Curr. Opin. Food Sci","volume":"2","issue":null,"page":"58\u201370"}]

[{"id":3563,"citationNumber":"32.","type":"article-journal","title":"Selective cytotoxicity of luteolin and kaempferol on cancerous hepatocytes obtained from rat model of hepatocellular carcinoma: involvement of ROS-mediated mitochondrial targeting","DOI":null,"author":[{"given":"E.","family":"Seydi"},{"given":"A.","family":"Salimi"},{"given":"H.R.","family":"Rasekh"},{"given":"Z.","family":"Mohsenifar"},{"given":"J.","family":"Pourahmad"}],"issued":{"date-parts":["2018"]},"container-title":"Nutr. Cancer","volume":"70","issue":"4","page":"594\u2013604"}]

[{"id":3564,"citationNumber":"33.","type":"article-journal","title":"Rosemary-stimulated reduction of DNA strand breaks and FPG-sensitive sites in mammalian cells treated with H2O2 or visible light-excited Methylene Blue","DOI":null,"author":[{"given":"D.","family":"Slame\u0148ov\u00e1"},{"given":"K.","family":"Kubo\u0161kov\u00e1"},{"given":"E.","family":"Horv\u00e1thov\u00e1"},{"given":"S.","family":"Robichov\u00e1"}],"issued":{"date-parts":["2002"]},"container-title":"Cancer Lett","volume":"177","issue":"2","page":"145\u201353"}]

[{"id":3565,"citationNumber":"34.","type":"article-journal","title":"Antiproliferation effect of rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro","DOI":null,"author":[{"given":"J.","family":"Tai"},{"given":"S.","family":"Cheung"},{"given":"M.","family":"Wu"},{"given":"D.","family":"Hasman"}],"issued":{"date-parts":["2012"]},"container-title":"Phytomedicine","volume":"19","issue":"5","page":"436\u201343"}]

[{"id":3566,"citationNumber":"35.","type":"article-journal","title":"Enhanced phenolic diterpenes antioxidant levels through non-transgenic approaches","DOI":null,"author":[{"given":"T.","family":"Tounekti"},{"given":"S.","family":"Munn\u00e9-Bosch"}],"issued":{"date-parts":["2012"]},"container-title":"Crit. Rev. Plant Sci","volume":"31","issue":"6","page":"505\u201319"}]

[{"id":3567,"citationNumber":"36.","type":"article-journal","title":"Cultural system affects fruit quality and antioxidant capacity in strawberries","DOI":null,"author":[{"given":"S.Y.","family":"Wang"},{"given":"W.","family":"Zheng"},{"given":"G.J.","family":"Galletta"}],"issued":{"date-parts":["2002"]},"container-title":"J. Agri. Food Chem","volume":"50","issue":"22","page":"6534\u20136542"}]

[{"id":3568,"citationNumber":"37.","type":"article-journal","title":"Caffeic acid phenethyl ester induces apoptosis by inhibition of NF\u03baB and activation of Fas in human breast cancer MCF-7 cells","DOI":null,"author":[{"given":"M.","family":"Watabe"},{"given":"K.","family":"Hishikawa"},{"given":"A.","family":"Takayanagi"},{"given":"N.","family":"Shimizu"},{"given":"T.","family":"Nakaki"}],"issued":{"date-parts":["2004"]},"container-title":"J. Biol. Chem","volume":"279","issue":"7","page":"6017\u20136026"}]

[{"id":3569,"citationNumber":"38.","type":"article-journal","title":"Inhibitory effects of rosemary extracts, carnosic acid and rosmarinic acid on the growth of various human cancer cell lines","DOI":null,"author":[{"given":"O.","family":"Yesil-Celiktas"},{"given":"C.","family":"Sevimli"},{"given":"E.","family":"Bedir"},{"given":"F.","family":"Vardar-Sukan"}],"issued":{"date-parts":["2010"]},"container-title":"Plant Foods Hum. Nutr","volume":"65","issue":"2","page":"158\u201363"}]

Citation

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 

Article metrics

Google scholar: See link

The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.