Investigation of cytotoxic and genotoxic potential of Cinnamomum cassia bark water extract

Year 2014, Volume: 4 Issue: 1, 17 - 23, 25.04.2014

Sumru Sozer Karadagli Borte Agrap Ferzan Lermioglu Erciyas

Abstract

Objective: Recently many investigations on cinnamon have focused on its powerful antioxidant activity due to its rich polyphenol content. Polyphenols have also been reported to act as pro-oxidants, causing oxidative strand breaks in DNA. In the present study, we investigated the cytotoxic and genotoxic potential of Cinnamomum cassia water extract in human peripheral blood lymphocytes. 

Methods: Cinnamomum cassia water extract was prepared from grounded bark of cinnamon by maceration with ultrapure water for 72 h. Cytotoxicity of the extract on lymphocytes was determined by WST-1 assay. Alkaline Comet assay was conducted to evaluate the DNA damaging potential of the extract. DNA damage was expressed as DNA percentage in the tail and tail moment. 

Results: The viability of lymphocytes was decreased by treatment with the extract for 24 h, as a concentration-dependent manner. At the concentrations ?400 µg/ml, the extract induced significant DNA damage compared to negative control.

Conclusion: Our results show the cytotoxic and genotoxic potential of Cinnamomum cassia bark water extract in vitro. This finding seems a significant safety concern, particularly in high doses or long term use of the extract, and therefore needs to be clarified by in vivo studies.

Key words: Cinnamomum cassia, alkaline Comet assay, cytotoxicity, pro-oxidant activity

Keywords

Cinnamomum cassia, alkaline Comet assay, cytotoxicity, pro-oxidant activity

Cinnamomum cassia kabuğu su ekstresinin sitotoksik ve genotoksik potansiyelinin araştırılması

Abstract

Amaç: Son zamanlarda, tarçın ile ilgili çalışmalar zengin polifenol içeriğine bağlı antioksidan aktivitesi üzerinde yoğunlaşmıştır. Polifenollerin aynı zamanda pro-oksidan olarak hareket ettikleri ve DNA’da oksidatif zincir kırıklarına neden oldukları bildirilmiştir. Bu çalışmada Cinnamomum cassia su ekstresinin insan periferal kan lenfositlerindeki sitotoksik ve genotoksik potansiyelini araştırdık. 

Yöntemler: Cinnamomum cassia su ekstresi, toz haline getirilmiş tarçın kabuğunun ultra saf suda 72 saat maserasyonu ile hazırlandı. Ekstrenin lenfositlerdeki sitotoksik etkisi WST-1 yöntemi ile araştırıldı. Ekstrenin DNA’da hasar oluşturucu potansiyelini değerlendirmek için alkali Komet yöntemi uygulandı. DNA hasarı kuyruk DNA yüzdesi ve kuyruk momenti şeklinde ifade edildi.

Bulgular: Lenfositlerin canlılığı ekstre ile 24 saat muamele sonrası konsantrasyona bağımlı olarak azaldı. Ekstre ?400 µg/ml konsantrasyonlarda negatif kontrole göre anlamlı düzeyde DNA hasarına neden oldu. 

Sonuç: Çalışma sonuçlarımız Cinnamomum cassia kabuğu su ekstresinin in vitro olarak sitotoksik ve genotoksik etki potansiyelini göstermektedir. Ekstrenin özellikle yüksek dozlarda ya da uzun süreli kullanımında güvenliliği açısından bu bulgu önemli görünmektedir ve bu nedenle in vivo çalışmalarla aydınlatılmalıdır.

Anahtar Kelimeler : Cinnamomum cassia, alkali Komet yöntemi, sitotoksisite, pro-oksidan aktivite

Keywords

Cinnamomum cassia, alkali Komet yöntemi, sitotoksisite, pro-oksidan aktivite

References

• Council of Scientific and Industrial Research, New Delhi, India. The Wealth of India. 1992; 3.
• Lee R, Balick MJ, Sweet wood — Cinnamon and its importance as a spice and medicine Explore: Explore. 2005;1(1):61-64.
• Gruenwald J, Freder J, Armbruester N. Cinnamon and Health. Crit Rev Food Sci Nutr. 2010; 50; 9:822-834.
• Kwon HK, Jeon WK, Hwang JS, Lee CG, So JS, Park JA, Ko BS, Im SH.Cinnamon extract suppresses tumor progression by modulating angiogenesis and the effector function of CD8+ T cells. Cancer Lett. 2009;278:174-182.
• Anderson RA. Chromium and polyphenols from cinnamon improve insulin sensitivity. Proceed Nutr Soc. 2008;67:48–53.
• Schoene NW, Kelly MA, Polansky MM, Anderson RA. Watersoluble polymeric polyphenols from cinnamon inhibit proliferation and alter cell cycle distribution patterns of hematologic tumor cell lines. Cancer Lett. 2005; 230:134-140.
• Kamei T, Kumano H, Iwata K, Nariai Y, Matsumoto T. The effect of a traditional Chinese prescription for a case of lung carcinoma. J Alternat Complemen Med. 2000;6:557-559.
• Singh R, Koppikar SJ, Paul P, Gilda S, Paradkar AR, Kaul-Ghanekar R. Comparative analysis of cytotoxic effect of aqueous cinnamon extract from Cinnamomum zeylanicum bark with commercial cinnamaldehyde on various cell lines. Phar Bio. 2009; 47(12):1174-1179.
• Luo Q, Wang SM, Lu Q, Luo J, Cheng YX. Identification of compounds from the water soluble extract of Cinnamomum cassia barks and their inhibitory effects against high-glucose-induced mesangial cells. Molecules. 2013;18:10930-10943.
• Wang YH, Avula B, Nanayakkara NP, Zhao J, Khan IA. Cassia cinnamon as a source of coumarin in cinnamon-flavored food and food supplements in the United States. J Agric Food Chem. 2013; 61(18):4470-4476.
• Cao H, Urban JF Jr. Anderson RA. Cinnamon polyphenol extract affects immune responses by regulating anti- and proinflammatory and glucose transporter gene expression in mouse macrophages. J Nutr. 2008; 138(5):833-840.
• Wondrak GT, Villeneuve NF, Lamore SD, Bause AS, Jiang Tao Z, Donna D. The cinnamon-derived dietary factor cinnamic aldehyde activates the Nrf2-dependent antioxidant response in human epithelial colon cells. Molecules. 2010; 15 (5):3338-3355.
• Qin B, Dawson HD, Schoene NW, Polansky MM, Anderson RA. Cinnamon polyphenols regulate multiple metabolic pathways involved in insulin signaling and intestinal lipoprotein metabolism of small intestinal enterocytes. Nutrition. 2012;28(11-12):1172-1179.
• Anderson RA, Broadhurst CL, Polansky MM, Schmidt WF, Khan A, Flanagan VP, Schoene NW, Graves DJ. Isolation and characterization of polyphenol type-A polymers from cinnamon with insulin-like biological activity. J Agric Food Chem. 2004;14;52(1):65-70.
• Yordi EG, Pérez EM, Matos MJ, Villares EU. Antioxidant and ProOxidant Effects of polyphenolic compounds and structure-activity relationship evidence. In Bouayed J. ed. Nutrition, Well-Being and Health. InTech; 2012. p. 23-48.
• Tabak M, Armon R, Neeman I. Cinnamon extracts’ inhibitory effect on Helicobacter pylori. J Ethnopharm. 1999;67:269-277.
• Qin B, Panickar KS, Anderson RA. Cinnamon: potential role in the prevention of insulin resistance, metabolic syndrome, and type 2 diabetes. J Diabetes Sci Technol. 2010;4(3):685-693.
• Hirose M, Takesada Y, Tanaka H, Tamano S, Kato T, Shirai T. Carcinogenicity of antioxidants BHA, caffeic acid, sesamol, 4-methoxyphenol and catechol at low doses, either alone or in combination, and modulation of their effects in a rat medium-term multi-organ carcinogenesis model. Carcinogenesis. 1998;19:207-212. Snyder RD, Gillies PJ. Evaluation of the clastogenic, DNA intercalative, and topoisomerase II-interactive properties of bioflavonoids in Chinese hamster V79 cells. Environ Mol Mutagen. 2002; 40:266-276.
• Catterall F, Souquet JM, Cheynier V, de Pascual-Teresa S, SantosBuelga C, Clifford MN, Ioannides C. Differential modulation of the genotoxicity of food carcinogens by naturally occurring monomeric and dimeric polyphenolics. Environ Mol Mutagen. 2000;35:86-98.
• Doyle A, Griffiths JB, Newell DG. Cell and Tissue Culture: Laboratory Procedures, John Wiley & Sons, Inc., Chichester, England 1995.
• Collins AR, Dobson VL, Dusinska M, Kenned G, Stetina R. The Comet Assay: what can it really tell us? Mutat Res. 1997; 375(2):183–193.
• Singh NP, Mc Coy MT, Tice RP, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988; 175(1):184-191.
• Wong VWC, Szeto YT, Collins AR, Benzie IFF. The Comet assay: a biomonitoring tool for nutraceutical research. Curr Topics Nutr Res. 2005;3:1-14.
• McKevith B, Kelly C, Stanner S, Hughes J, Buttriss J. The Food Standards Agency’s antioxidants in food programme -a summary. J Hum Nutr Dietet. 2003; 16:257-263.
• Yen GC, Duh PD, Tsai HL, Huang SL. Pro-oxidative properties of flavonoids in human lymphocytes. Biosci Biotechnol Biochem. 2003; 67(6):1215-1222.
• New EJ, Congreve A, Parker D. Definition of the uptake mechanism and sub-cellular localization profile of emissive lanthanide complexes as cellular optical probes. Chem Sci. 2010; 1: 111-118.
• Koppikar SJ, Choudhari AS, Suryavanshi SA, Kumari S, Chattopadhyay S, Kaul-Ghanekar R. Aqueous cinnamon extract (ACE-c) from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa) through loss of mitochondrial membrane potential. BMC Cancer. 2010; 10:210-221.
• Kwon HK, Hwang JS, So JS, Lee CG, Sahoo A, Ryu JH, Jeon WK, Ko BS, Im CR, Lee SH, Park ZY, Im SH. Cinnamon extract induces tumor cell death through inhibition of NFκB and AP1. BMC Cancer. 2010; 10:392400.
• Anderson D, Hambly RJ, Yu TW, Thomasoni F, Shuker DEG. The effect of potassium diazoacetate on human peripheral lymphocytes, human adenocarcinoma colon Caco-2 cells, and rat primary colon cells in the Comet assay. Teratog Carcinog Mutagen. 1999; 19:137– 1
• Kassie F, Parzefall W, Knasmüller S. Single cell gel electrophoresis assay: a new technique for human biomonitoring studies. Mutat Res. 2000; 463:13-31.
• Dai J, Mumper RJ. Plant Phenolics: Extraction, analysis and their antioxidant and anticancer properties. Molecules. 2010; 15: 731373
• Sozer Karadagli S, Agrap B, Lermioglu Erciyas F. Investigation of the Protective Effect of Cinnamomum cassia Bark Extract Against H 2 O 2 -Induced Oxidative DNA Damage in Human Peripheral Blood Lymphocytes and Antioxidant activity. Marmara Pharm J. 2014; 18:43-48.
• Lambert J, Elias R. The antioxidant and pro-oxidant activities of green tea polyphenols: A role in cancer prevention. Arch Biochem Biophys. 2010; 501(1): 65-72.
• Sharma N, Trikha P, Athar M, Raisuddin S. Inhibition of benzo[a]pyreneand cyclophoshamide-induced mutagenicity by Cinnamomum cassia. Mutat Res. 2001; 480-481:179-188.