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Inhibitory Effects of Tualang Honey on Experimental Breast Cancer in Rats: A Preliminary Study

  • Kadir, Erazuliana Abd (Pharmacology Department, School of Medical Sciences, Universiti Sains Malaysia) ;
  • Sulaiman, Siti Amrah (Pharmacology Department, School of Medical Sciences, Universiti Sains Malaysia) ;
  • Yahya, Nurul Khaiza (Immunology Department, School of Medical Sciences, Universiti Sains Malaysia) ;
  • Othman, Nor Hayati (Pathology Department, School of Medical Sciences, Universiti Sains Malaysia)
  • Published : 2013.04.30

Abstract

The study was conducted to determine the effect of Malaysian jungle Tualang Honey (TH) on development of breast cancer induced by the carcinogen 7,12-dimethylbenz(${\alpha}$)anthracene (DMBA) in rats. Forty nulliparous female Sprague-Dawley rats were given 80 mg/kg DMBA then randomly divided into four groups: Group 1 served as a Control while Groups 2, 3 and 4 received 0.2, 1.0 or 2.0 g/kg bodyweight/day of TH, respectively, for 150 days. Results showed that breast cancers in the TH-treated groups had slower size increment and smaller mean tumor size (${\leq}2cm^3$) compared to Controls (${\leq}8cm^3$). The number of cancers developing in TH-treated groups was also significantly fewer (P<0.05). Histological grading showed majority of TH-treated group cancers to be of grade 1 and 2 compared to grade 3 in controls. There was an increasing trend of apoptotic index (AI) seen in TH-treated groups with increasing dosage of Tualang Honey, however, the mean AI values of all TH-treated groups were not significantly different from the Control value (p>0.05). In conclusion, Tualang Honey exerted positive modulation effects on DMBA-induced breast cancers in rats in this preliminary study.

Keywords

References

  1. Ball DW (2007). The chemical composition of honey. J Chemical Education, 84, 1643-6. https://doi.org/10.1021/ed084p1643
  2. Barrett JC (1993). Mechanisms of multistep carcinogenesis and carcinogen risk assessment. Environ Health Perspect, 100, 9-20. https://doi.org/10.1289/ehp.931009
  3. Burstein HJ, Polyak K, Wong JS, et al (2004). Ductal carcinoma in situ of the breast. N Engl J Med, 350, 1430-41. https://doi.org/10.1056/NEJMra031301
  4. Costa I, Solanas M, Escrich E (2002). Histopathologic characterization of mammary neoplastic lesions induced with 7,12 dimethylbenz(alpha)anthracene in the rat: a comparative analysis with human breast tumors. Arch Pathol Lab Med, 126, 915-27.
  5. Dalton LW, Pinder SE, Elston CE, et al (2000). Histologic grading of breast cancer: Linkage of patient outcome with level of pathologist agreement. Mod Pathol, 13, 730-5. https://doi.org/10.1038/modpathol.3880126
  6. Dias M, Cabrita S, Sousa E, et al (1999). Benign and malignant mammary tumors induced by DMBA in female Wistar rats. Eur J Gynaecol Oncol, 20, 285-8.
  7. Fauzi AN, Norazmi MN, Yaacob NS (2010). Tualang honey induces apoptosis and disrupts the mitochondrial membrane potential of human breast and cervical cancer cell lines. Food and Chemical Toxicology, In Press.
  8. Ghashm A, Othman N, Khattak M, et al (2010). Antiproliferative effect of tualang honey on oral squamous cell carcinoma and osteosarcoma cell lines. BMC Complementary and Alternative Medicine, 10, 49.
  9. Gribel NV, Pashinskii VG (1990). The antitumor properties of honey. Vopr Onkol, 36, 704-9.
  10. Harvey JM, Klerk NHD, Robbins PD, et al (1995). Histological grading of breast cancer: a study of reproducibility of consensus grading. The Breast, 4, 297-300. https://doi.org/10.1016/S0960-9776(95)80007-7
  11. Hsu YL, Kuo PL, Lin CC (2004a). Acacetin inhibits the proliferation of Hep G2 by blocking cell cycle progression and inducing apoptosis. Biochem Pharmacol, 67, 823-9. https://doi.org/10.1016/j.bcp.2003.09.042
  12. Hsu YL, Kuo PL, Liu CF, et al (2004b). Acacetin-induced cell cycle arrest and apoptosis in human non-small cell lung cancer A549 cells. Cancer Lett, 212, 53-60. https://doi.org/10.1016/j.canlet.2004.02.019
  13. Hwang HJ, Park HJ, Chung HJ, et al (2006). Inhibitory effects of caffeic acid phenethyl ester on cancer cell metastasis mediated by the down-regulation of matrix metalloproteinase expression in human HT1080 fibrosarcoma cells. J Nutr Biochem, 17, 356-62. https://doi.org/10.1016/j.jnutbio.2005.08.009
  14. Indap M, Radhika S, Motiwale L, et al (2006). Quercetin: Antitumor activity and pharmacological manipulations for increased therapeutic gains. Indian J Pharmaceutical Sci, 68, 465-9. https://doi.org/10.4103/0250-474X.27819
  15. Iurlina MO, Saiz, AI, Fritz R, et al (2009). Major flavonoids of Argentinean honeys. Optimisation of the extraction method and analysis of their content in relationship to the geographical source of honeys. Food Chemistry, 115, 1141-9. https://doi.org/10.1016/j.foodchem.2009.01.003
  16. Jaganathan SK, Mahitosh M (2009). Antiproliferative effects of honey and of its polyphenols: a review. J Biomedicine and Biotechnology, 13.
  17. Kritchevsky D, Weber MM, Klurfeld DM (1984). Dietary fat versus caloric content in initiation and promotion of 7,12-dimethylbenz(${\alpha}$)anthracene-induced mammary tumorigenesis in rats. Cancer Res, 44, 3174-7.
  18. Lai H, Singh NP (2006). Oral artemisinin prevents and delays the development of 7,12-dimethylbenz[${\alpha}$]anthracene (DMBA)-induced breast cancer in the rat. Cancer Lett, 231, 43-8. https://doi.org/10.1016/j.canlet.2005.01.019
  19. Maiorana A, Gullino PM (1978). Acquisition of angiogenic capacity and neoplastic transformation in the rat mammary gland. Cancer Res, 38, 4409-14.
  20. Makrilia N, Lappa T, Xyla V, et al (2009). The role of angiogenesis in solid tumours: an overview. Eur J Int Med,20, 663-71. https://doi.org/10.1016/j.ejim.2009.07.009
  21. Mehta RG (2000). Experimental basis for the prevention of breast cancer. Eur J Cancer, 36, 1275-82. https://doi.org/10.1016/S0959-8049(00)00100-3
  22. Mohamed M, Sirajudeen K, Swamy M, Yaacob NS, Sulaiman SA (2010). Studies on the antioxidant properties of tualang honey of Malaysia. Afr J Tradit Complement Altern Med, 7, 59-63. https://doi.org/10.1625/jcam.7.59
  23. Mukhopadhyay S, Ballard B, Mukherjee S, et al (2006). Beneficial effects of soy protein in the initiation and progression against dimethylbenz [${\alpha}$] anthracene-induced breast tumors in female rats. Molecular and Cellular Biochemistry, 290, 169-76. https://doi.org/10.1007/s11010-006-9184-9
  24. Nasir NA, Halim A, Singh KK, et al (2010). Antibacterial properties of tualang honey and its effect in burn wound management: a comparative study. BMC Complementary and Alternative Medicine, 10, 31. https://doi.org/10.1186/1472-6882-10-31
  25. Pyrzynska K, Biesaga M (2009). Analysis of phenolic acids and flavonoids in honey. TrAC Trends in Analytical Chemistry, 28, 893-902. https://doi.org/10.1016/j.trac.2009.03.015
  26. Russo J, Russo IH (2000). Atlas and histologic classification of tumors of the rat mammary gland. J Mammary Gland Biol Neoplasia, 5, 187-200. https://doi.org/10.1023/A:1026443305758
  27. Silverstein MJ (1998). Ductal carcinoma in situ of the breast. BMJ, 317, 734-9. https://doi.org/10.1136/bmj.317.7160.734
  28. Tan HT, Abdul Rahman R, Gan SH, et al (2009). The antibacterial properties of Malaysian Tualang honey against wound and enteric microorganisms in comparison to Manuka honey. BMC Complementary and Alternative Medicine, 9, 1-8. https://doi.org/10.1186/1472-6882-9-1
  29. Toi M, Kondo S, Suzuki H, et al (1996). Quantitative analysis of vascular endothelial growth factor in primary breast cancer. Cancer, 77, 1101-6. https://doi.org/10.1002/(SICI)1097-0142(19960315)77:6<1101::AID-CNCR15>3.0.CO;2-5
  30. Tosetti F, Ferrari N, De Flora S, et al (2002). Angioprevention': angiogenesis is a common and key target for cancer chemopreventive agents. Faseb J, 16, 2-14. https://doi.org/10.1096/fj.01-0300rev
  31. Valko M, Leibfritz D, Moncol J, et al (2007). Free radicals and antioxidants in normal physiological functions and human disease. The Int J Biochemistry and Cell Biology, 39, 44-84. https://doi.org/10.1016/j.biocel.2006.07.001
  32. Volpi A, Bacci F, Paradiso A, et al (2004). Prognostic relevance of histological grade and its components in node-negative breast cancer patients. Mod Pathol, 17, 1038-44. https://doi.org/10.1038/modpathol.3800161
  33. Way TD, Kao MC, Lin JK (2004). Apigenin induces apoptosis through proteasomal degradation of HER2/neu in HER2/neu-overexpressing breast cancer cells via the phosphatidylinositol 3-kinase/Akt-dependent pathway. J Biol Chem, 279, 4479-89.
  34. Welsh CW (1994). Interrelationship between dietary lipids and calories and experimental mammary gland tumorigenesis. Cancer, 74, 1055-62. https://doi.org/10.1002/1097-0142(19940801)74:3+<1055::AID-CNCR2820741513>3.0.CO;2-0
  35. Woo KJ, Jeong YJ, Park JW, et al (2004). Chrysin-induced apoptosis is mediated through caspase activation and Akt inactivation in U937 leukemia cells. Biochem Biophys Res Commun, 325, 1215-22. https://doi.org/10.1016/j.bbrc.2004.09.225
  36. Yao L, Datta N, Tomas-Barberan FA, et al (2003). Flavonoids, phenolic acids and abscisic acid in Australian and New Zealand Leptospermum honeys. Food Chemistry, 81, 159-68. https://doi.org/10.1016/S0308-8146(02)00388-6

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