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http://dx.doi.org/10.7314/APJCP.2012.13.4.1605

Gelam and Nenas Honeys Inhibit Proliferation of HT 29 Colon Cancer Cells by Inducing DNA Damage and Apoptosis while Suppressing Inflammation  

Wen, Christinal Teh Pey (Department of Biomedical Science, Faculty of Allied Health Sciences, Universiti Kebangsaan Malaysia)
Hussein, Saba Zuhair (Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia)
Abdullah, Shailah (Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia)
Karim, Norwahidah Abdul (Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia)
Makpol, Suzana (Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia)
Yusof, Yasmin Anum Mohd (Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.4, 2012 , pp. 1605-1610 More about this Journal
Abstract
Gelam and Nenas monofloral honeys were investigated in this study for their chemopreventive effects against HT 29 colon cancer cells. MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolim) assays showed more effective inhibition of colon cancer cells proliferation by Gelam honey with $IC_{50}$ values of 39.0 mg/ml and 85.5 mg/ml respectively after 24 hours of treatment. Alkali comet assays revealed both honeys increased DNA damage significantly in a dose dependent manner. In addition, annexin V-FITC/PI flow cytometry demonstrated that at $IC_{50}$ concentrations and above, both Gelam and Nenas honeys induced apoptosis significantlyat values higher than for necrosis (p<0.05). Measurement of prostaglandin $E_2$ ($PGE_2$) confirmed that Gelam and Nenas honeys reduced its production in $H_2O_2$ inflammation-induced colon cancer cells. In conclusion, our study indicated and confirmed that both Gelam and Nenas honeys are capable of suppressing the growth of HT 29 colon cancer cells by inducing apoptosis and suppressing inflammation.
Keywords
Gelam honey; nenas honey, HT29 cells; antitumor; anti-inflammatory; apoptosis; DNA damage;
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1 Aljadi AM, Kamaruddin MY (2002). Evaluation of the phenolic content and antioxidant capacities of two Malaysian floral honeys. Food Chem, 85, 513-8.
2 Aljadi AM, Kamaruddin MY (2003). Isolation and Identification of phenolic acids in Malaysian honey with antibacterial properties. Turk J Med Sci, 33, 229-36.
3 American Cancer Society (2011). Detailed guide: colon and rectum cancer. What are the risk factors for colon cancer? Download from http://209.135.47.118/docroot/CRI/content/CRI_2_4_2X_ Accessed on 24 March 2011.
4 Banu N, Buda A, Chell S, et al (2007). Inhibits colon cancer cell migration Inhibition of COX-2 with NS 398 decreases colon cancer cell motility through blocking epidermal growth factor receptor transactivation: possibilities for combination therapy. Cell Prolif, 40, 768-79.   DOI
5 Belousova AK (1977). The mechanisms of action of antitumor compounds. Natl Cancer Inst Monogr, 45, 183-93.
6 Burden DA, Osheroff N (1998). Mechanism of action of eukaryotic topoisomerase II and drugs targeted to the enzyme. Biochim Biophys Acta, 1400, 139-54.   DOI   ScienceOn
7 Chambers J (2006). Topical manuka honey for MRSAcontaminated skin ulcers. Palliative Med, 20, 557.   DOI
8 Cherchi A, Spanedda L, Tuberoso C, et al (1994). Solid phase extraction and high-performance liquid chromatographic determination of organic acids in honey. J Chromat A, 669, 59-64.   DOI
9 Fauzi AN, Norazmi MN, Yaacob NS (2011). Tualang honey induces apoptosis and disrupts the mitochondrial membrane potential of human breast and cervical cancer cell lines. Food Chem Toxicol, 49, 871-8.   DOI
10 Ghashm AA, Othman NH, Khattak MN, et al (2010). Antiproliferative effect of Tualang honey on oral squamous cell carcinoma and osteosarcoma cell lines. BMC Compl and Alt Med, 10, 49.
11 Hussein SZ, Makpol S, Abdul Karim N, et al (2011). Antioxidant Capacities and Total Phenolic Contents Increase with Gamma Irradiation in Two Types of Malaysian Honey. Molecules, 16, 6378-95.   DOI
12 Issa AY, Volate SR, Wargovich MJ (2006). Critical review the role of phytochemicals in inhibition of cancer and inflammation: New directions and perspectives. J Food Composition and Analysis, 19, 405-19.   DOI
13 Jaganathan S, Mandal M (2009a). Honey constituents and their apoptotic effect in colon cancer cells. J ApiProduct and Apimed Sci, 1, 29-36.   DOI
14 Jaganathan S, Mandal M (2009b). Involvement of non protein thiols, mitochondrial dysfunction, reactive oxygen species and p53 in honey-induces apoptosis. Invest New Drugs, ?, 1-10.
15 Jaganathan SK, Mazumdar A, Mondhe D, et al (2010). Apoptotic effect of eugenol in human colon cancer cell lines. Cell Biol Int, 35, 607-15.
16 Kassim M, Achoui M, Mansor M, et al (2010a). The inhibitory effects of Gelam Honey and its extracts on nitric oxide and prostaglandin $E_{2}$ in inflammatory tissues. Fitoterapia, 81, 1196-201.   DOI   ScienceOn
17 Klatz R, Glodman R (2003). The New Antiaging Revolution, 3rd ed. New Jersey, Basic Health Publication, Inc, pp 332-4.
18 Kassim M, Achoui M, Mansor M, et al (2010b). Ellagic acid, phenolic acids, and flavonoids in Malaysian honey extracts demonstrate in vitro anti-inflammatory activity. Nutr Res, 30, 650-9.   DOI
19 Kawai N, Tsujii M, Tsuji S (2002). Cyclooxygenases and colon cancer. Prostagland Other Lipid Mediators, 68, 187-96.   DOI
20 Khalil MI, Sulaiman SA (2010). The potential role of honey and its polyphenols in preventing heart diseases: a review. Afr J Tradit Complement Altern Med, 7, 315-21.
21 Kucuk M, Kolayli S, Karaoglu S, et al (2007). Biological activities and chemical composition of three honeys of different types from Anatolia. Food Chem, 100: 526-34.   DOI
22 Martos I, Cossentini M, Ferreres F, et al (1997). Flavonoid composition of Tunisian honeys and propolis. J Agr Food Chem, 45, 2824-9.   DOI   ScienceOn
23 Mobarok AM, Al Swaye OA (2003). Honey potentiates the gastric protection effects of sucralfate against ammoniainduced gastric lesions in rats. Saudi J Gastroenterol, 9, 117-23.
24 Molan PC (2009). Honey: antimicrobial and role in disease management. In 'New Strategies Combating Bacterial Infection' (eds. Iqbal Ahmad, Farrukh Aqil); Weinheim:Wiley-Blackwell, pp. 229-54.
25 Molan PC (2006). The Evidence Supporting the Use of Honey as a Wound Dressing. Int J of Lower Extremity Wounds, 5, 40-54.   DOI   ScienceOn
26 Mossman T (1983). Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods, 65, 55-63.   DOI   ScienceOn
27 Poole E, Bigler J, Whitton J, et al (2006). Prostacyclin synthase and arachidonate 5-lipoxygenase polymorphisms and risk of colorectal polyps. Cancer Epid Bio & Prev, 15, 502-8.   DOI   ScienceOn
28 National Cancer Registry (2006). Malaysian Cancer Statistics-Data and Figure Peninsular Malaysia: 1-112.
29 Pichichero E, Cicconi R, Mattei M, et al (2011). Chrysin-induced apoptosis is mediated through p38 and Bax activation in B16-F1 and A375 melanoma cells. Int J Oncol, 38, 473-83.
30 Ploski JE, Aplan PD (2001). Characterization of DNA fragmentation events caused by genotoxic and non-genotoxic agents. Mutat Res, 473, 169-80.   DOI
31 Renoa F, Bajb G, Surico N, et al (2004). Exogenous prostaglandin E2 inhibits TPA-induced matrix metalloproteinase-9 production in MCF-7 cells. Prostaglandins & Other Lipid Mediators, 73, 237-47.   DOI
32 Russo A, Cardile V, Sanchez F, et al (2004). Chilean propolis: antioxidant activity and antiproliferative action in human tumor cell lines. J Life Sci, 76, 545-58.   DOI   ScienceOn
33 Singh NP, McCoy MT, Tice RR, et al (1988). A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res, 175, 184-91.   DOI   ScienceOn
34 Subrahmanyam M, Sahapure AG, Nagane NS, et al (2001). Effects of topical application of honey on burn wound healing. Annals of Burns and Fire Disasters, 115, 1-3.
35 Sun SY, Hail NJr, Lotan R (2004). Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst, 96, 662-72.   DOI   ScienceOn
36 Vodovotz Y, Constantineb G, Rubin J, et al (2009). Mechanistic simulations of inflammation: Current state and future prospects. Mathemat Biosci, 217, 1-10.   DOI
37 Surh Y-J, Chun K-S, Cha H-H, et al (2001). Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-$\kappa B$ activation. Mutation Res, 480, 243-68.   DOI   ScienceOn
38 Takahashi T, Takasuka N, Iigo M, et al (2004). Isoliquiritigenin, a flavonoid from licorice, reduces prostaglandin $E_{2}$ and nitric oxide, causes apoptosis, and suppresses aberrant crypt foci development. Cancer Sci, 95, 448-53.   DOI   ScienceOn
39 USDA National Nutrient Database for Standard Reference (2011). Honey. Download from http://www.nal.usda.gov/fnic/foodcomp/cgi-bin/list_nut_edit.pl. Accessed on 21 March 2011.
40 White JW, Crane E (1975). Honey a Comprehensive Survey. London: Heinemann.
41 Wollgast J, Anklam E (2000). Review on polyphenols in Theobroma cacao: changes in composition during the manufacture of chocolate and methodology for identification and quantification. Food Res Int, 33, 423-47.   DOI
42 Yuen JWM, Gohel MDI (2008). The dual roles of Ganoderma antioxidants on urothelial cell DNA under carcinogenic attack. J Ethnopharmacol, 118, 324-30.   DOI
43 Zoltan G (2008). Mechanisms of toxicity. In 'The Basic Science of Poisons: Casarett and Doull's Toxicology. 7th edn' (edn Klaassen CD); New York, McGraw-Hill, pp. 45-106.