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DOI: 10.1055/s-0035-1558083
Essential Oil from Myrica rubra Leaves Potentiated Antiproliferative and Prooxidative Effect of Doxorubicin and its Accumulation in Intestinal Cancer Cells
Publication History
received 16 April 2015
revised 05 August 2015
accepted 10 August 2015
Publication Date:
20 October 2015 (online)
Abstract
Essential oil from the leaves of Myrica rubra, a subtropical Asian fruit tree traditionally used in folk medicines, has a significant antiproliferative effect in several intestinal cancer cell lines. Doxorubicin belongs to the most important cytostatics used in cancer therapy. The present study was designed to evaluate the effects of defined essential oil from M. rubra leaves on efficacy, prooxidative effect, and accumulation of doxorubicin in cancer cell lines and in non-cancerous cells. For this purpose, intestinal adenocarcinoma CaCo2 cells were used. Human fibroblasts (periodontal ligament) and a primary culture of rat hepatocytes served as models of non-cancerous cells. The results showed that the sole essential oil from M. rubra has a strong prooxidative effect in cancer cells while it acts as a mild antioxidant in hepatocytes. Combined with doxorubicin, the essential oil enhanced the antiproliferative and prooxidative effects of doxorubicin in cancer cells. At higher concentrations, synergism of doxorubicin and essential oil from M. rubra was proved. In non-cancerous cells, the essential oil did not affect the toxicity of doxorubicin and the doxorubicin-mediated reactive oxygen species formation. The essential oil increased the intracellular concentration of doxorubicin and enhanced selectively the doxorubicin accumulation in nuclei of cancer cells. Taken together, essential oil from M. rubra leaves could be able to improve the doxorubicin efficacy in cancer cells due to an increased reactive oxygen species production, and the doxorubicin accumulation in nuclei of cancer cells.
Key words
Myrica rubra - Myricaceae - cytotoxicity - ROS formation - drug penetration - CaCo2 cell line - hepatocytes - fibroblasts-
References
- 1 Kang W, Li Y, Xu Y, Jiang W, Tao Y. Characterization of aroma compounds in Chinese bayberry (Myrica rubra Sieb. et Zucc.) by gas chromatography mass spectrometry (GC-MS) and olfactometry (GC-O). J Food Sci 2012; 77: C1030-C1035
- 2 Tong Y, Zhou XM, Wang SJ, Yang Y, Cao YL. Analgesic activity of myricetin isolated from Myrica rubra Sieb. et Zucc. leaves. Arch Pharm Res 2009; 32: 527-533
- 3 Wang SJ, Tong Y, Lu S, Yang R, Liao X, Xu YF, Li X. Anti-inflammatory activity of myricetin isolated from Myrica rubra Sieb. et Zucc. leaves. Planta Med 2010; 76: 1492-1496
- 4 Kim HH, Oh MH, Park KJ, Heo JH, Lee MW. Anti-inflammatory activity of sulfate-containing phenolic compounds isolated from the leaves of Myrica rubra . Fitoterapia 2014; 92: 188-193
- 5 Sun C, Huang H, Xu C, Li X, Chen K. Biological activities of extracts from Chinese bayberry (Myrica rubra Sieb. et Zucc.): a review. Plant Foods Hum Nutr 2013; 68: 97-106
- 6 Yang LL, Chang CC, Chen LG, Wang CC. Antitumor principle constituents of Myrica rubra var. acuminata . J Agr Food Chem 2003; 51: 2974-2979
- 7 Sun C, Zheng Y, Chen Q, Tang X, Jiang M, Zhang J, Li X, Chen K. Purification and anti-tumour activity of cyanidin-3-O-glucoside from Chinese bayberry fruit. Food Chem 2012; 131: 1287-1294
- 8 Xu L, Gao J, Wang Y, Yu W, Zhao X, Yang X, Zhong Z, Qian ZM. Myrica rubra extracts protect the liver from CCl4-induced damage. Evid Based Complement Alternat Med 2011; 2011: 518302
- 9 Liu H, Qi X, Cao S, Li P. Protective effect of flavonoid extract from Chinese bayberry (Myrica rubra Sieb. et Zucc.) fruit on alcoholic liver oxidative injury in mice. J Nat Med 2014; 68: 521-529
- 10 Yang Z, Cao S, Zheng Y. Chinese bayberry fruit extract alleviates oxidative stress and prevents 1,2-dimethylhydrazine-induced aberrant crypt foci development in rat colon carcinogenesis. Food Chem 2011; 125: 701-705
- 11 Dai GH, Meng GM, Tong YL, Chen X, Ren ZM, Wang K, Yang F. Growth-inhibiting and apoptosis-inducing activities of myricanol from the bark of Myrica rubra in human lung adenocarcinoma A549 cells. Phytomedicine 2014; 21: 1490-1496
- 12 Langhansova L, Hanusova V, Rezek J, Stohanslova B, Ambroz M, Kralova V, Vanek T, Lou JD, Yun ZL, Yang J, Skalova L. Essential oil from Myrica rubra leaves inhibits cancer cell proliferation and induces apoptosis in several human intestinal lines. Ind Crops Prod 2014; 59: 20-26
- 13 el Hadri A, del Rio MAG, Sanz J, Coloma AG, Idaomar M, Ozonas BR, Gonzalez JB, Reus MIS. Cytotoxic activity of alpha-humulene and trans-caryophyllene from Salvia officinalis in animal and human tumor cells. An Real Acad Nal Farm 2010; 76: 343-356
- 14 Legault J, Dahl W, Debiton E, Pichette A, Madelmont JC. Antitumor activity of balsam fir oil: production of reactive oxygen species induced by alpha-humulene as possible mechanism of action. Planta Med 2003; 69: 402-407
- 15 Legault J, Pichette A. Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel. J Pharm Pharmacol 2007; 59: 1643-1647
- 16 Sylvestre M, Legault J, Dufour D, Pichette A. Chemical composition and anticancer activity of leaf essential oil of Myrica gale L. Phytomedicine 2005; 12: 299-304
- 17 Carvalho FS, Burgeiro A, Garcia R, Moreno AJ, Carvalho RA, Oliveira PJ. Doxorubicin-induced cardiotoxicity: from bioenergetic failure and cell death to cardiomyopathy. Med Res Rev 2014; 34: 106-135
- 18 Hanusova V, Bousova I, Skalova L. Possibilities to increase the effectiveness of doxorubicin in cancer cells killing. Drug Metab Rev 2011; 43: 540-557
- 19 Adorjan B, Buchbauer G. Biological properties of essential oils: an updated review. Flavour Frag J 2010; 25: 407-426
- 20 Bhalla Y, Gupta VK, Jaitak V. Anticancer activity of essential oils: a review. J Sci Food Agr 2013; 93: 3643-3653
- 21 Raut JS, Karuppayil SM. A status review on the medicinal properties of essential oils. Ind Crops Prod 2014; 62: 250-264
- 22 Krishnaiah YSR, Al-Saidan SM, Jayaram B. Effect of nerodilol, carvone and anethole on the in vitro transdermal delivery of selegiline hydrochloride. Pharmazie 2006; 61: 46-53
- 23 Saeedi M, Morteza-Semnani K. Penetration-enhancing effect of the essential oil and methanolic extract of Eryngium bungei on percutaneous absorption of piroxicam through rat skin. J Essent Oil Bear Pl 2009; 12: 728-741
- 24 Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev 2012; 64: 128-137
- 25 Bartikova H, Hanusova V, Skalova L, Ambroz M, Bousova I. Antioxidant, pro-oxidant and other biological activities of sesquiterpenes. Curr Top Med Chem 2014; 14: 2478-2494
- 26 Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res 2010; 70: 440-446
- 27 Mahmoud SS, Torchilin VP. Hormetic/cytotoxic effects of Nigella sativa seed alcoholic and aqueous extracts on mcf-7 breast cancer cells alone or in combination with doxorubicin. Cell Biochem Biophys 2013; 66: 451-460
- 28 Effenberger-Neidnicht K, Schobert R. Combinatorial effects of thymoquinone on the anti-cancer activity of doxorubicin. Cancer Chemother Pharmacol 2011; 67: 867-874
- 29 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: 625-630
- 30 Martin-Cordero C, Leon-Gonzalez AJ, Calderon-Montano JM, Burgos-Moron E, Lopez-Lazaro M. Pro-oxidant natural products as anticancer agents. Curr Drug Targets 2012; 13: 1006-1028
- 31 Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?. Nat Rev Drug Discov 2009; 8: 579-591
- 32 Li X, Fang P, Mai J, Choi ET, Wang H, Yang XF. Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers. J Hematol Oncol 2013; 6: 19
- 33 Erdogan A, Ozkan A. Effects of Thymus revolutus Célak essential oil and its two major components on Hep G2 cells membrane. Biologia 2013; 68: 105-111
- 34 Ni L, Shi WY. Composition and free radical scavenging activity of kernel oil from Torreya grandis, Carya Cathayensis and Myrica Rubra . Iran J Pharm Res 2014; 13: 221-226
- 35 Wang H, Joseph JA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 1999; 27: 612-616
- 36 Skarka A, Skarydova L, Stambergova H, Wsol V. Anthracyclines and their metabolism in human liver microsomes and the participation of the new microsomal carbonyl reductase. Chem Biol Interact 2011; 191: 66-74