Journal of Medical Research and Development          
Journal of Medical Research and Development(JMRD)
ISSN:2303-9345(Print)
ISSN:2303-9353(Online)
Frequency: Quarterly
Website: www.academicpub.org/jmrd/
Insulin Sensitivity Enhancement of the Mixture of Tinospora Crispa and Gelam (Melaleuca Cajuputi) Honey and Its Antiproliferative Activity on Hepatocellular Carcinoma, HepG2: A Preliminary Study
Full Paper(PDF, 404KB)
Abstract:
This study aims to investigate the effect of Tinosporacrispa and Gelam (Melaleucacajupati) honey mixture on human hepatocellular carcinoma (HepG2) and normal human hepatocytes(WRL-68) cell lines. Cell cytotoxicity was measured using MTS assay. The IC50obtained was 42.67% in HepG2 and none in the WRL-68. Western blotting showed an increment in phosphorylation of tyrosine (PY20), indicating induction of Caspase 3 apoptotic proteins, whereas, the gene product of insulin growth-like receptor (IGF-1R) was reduced, indicating cancer cell inhibition. It is concluded that the elevation of Caspase 3 and the inhibition of IGF-1R indicates the ability of this mixture to simultaneously promote apoptosis and sensitized insulin in HepG2 cells.
Keywords:Tinosporacrispa; Gelam Honey; Apoptosis; Cytotoxicity; Insulin Sensitivity; Hepg2; WRL-68
Author: Wan Iryani Wan Ismail1, Mohd Nazri Abu2, Muhammad Ashraf Mohd Salleh1, Nabilatul Hani Mohd Radzman1, Rosmadi Mohd Yusof1, Hamzah Fansuri Hassan2
1.Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia
2.Faculty of Health Sciences, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia
References:
  1. Mohammaed Qatanani and L. Mitchell A, "Mechanism of obesity-associated insulin resistance: many choices on the menu," Genes & Development, pp. 1443-1445, 2007.
  2. E. J. Gallagher, Y. Fierz, R. D. Ferguson, and D. LeRoith, "The pathway from diabetes and obesity to cancer, on the route to targeted therapy," Endocr Pract, vol. 16, pp. 864-73, 2010.
  3. P. K. Shah, "Innate immune pathway links obesity to insulin resistance," American Heart Association, 2007.
  4. Y. J. Surh, "Cancer chemoprevention with dietary phytochemicals," Nat Rev Cancer, vol. 3, pp. 768-80, 2003.
  5. E. Gonzalez, E. Flier, D. Molle, D. Accili, and T. E. McGraw, "Hyperinsulinemia leads to uncoupled insulin regulation of the GLUT4 glucose transporter and the FoxO1 transcription factor," Proc Natl Acad Sci U S A, vol. 108, pp. 10162-7, 2011.
  6. J.-R. Zhou, G. L. Blackburn, and W. A. Walker, "Symposium introduction: metabolic syndrome and the onset of cancer," The American Journal of Clinical Nutrition, vol. 86, pp. 817S-819S, September 1, 2007 2007.
  7. I. F. Godsland., "Insulin resistance and hyperinsulinemia in the development and progression of cancer," Clinical science, pp. 315-332, 2010.
  8. M. H. Shanik, Y. Xu, J. ?krha, R. Dankner, Y. Zick, and J. Roth, "Insulin Resistance and Hyperinsulinemia: Is hyperinsulinemia the cart or the horse?," Diabetes Care, vol. 31, pp. S262-S268, 2008.
  9. B. Balkau, H. S. Kahn, D. Courbon, E. Eschwege, and P. Ducimetiere, "Hyperinsulinemia predicts fatal liver cancer but is inversely associated with fatal cancer at some other sites: the Paris Prospective Study," Diabetes Care, vol. 24, pp. 843-9, 2001.
  10. T. Yoshikawa, Y. Noguchi, C. Doi, T. Makino, and K. Nomura, "Insulin resistance in patients with cancer: relationships with tumor site, tumor stage, body-weight loss, acute-phase response, and energy expenditure," Nutrition, vol. 17, pp. 590-593, 2001.
  11. A. C. Dweck and J.-P. Cavin, "Andawali (Tinospora crispa) – a review," Personal care megazine, vol. 7, pp. 1-3, 2006.
  12. S. Mohamad, N. M. Zin, H. A. Wahab, P. Ibrahim, S. F. Sulaiman, A. S. Zahariluddin, and S. S. Noor, "Antituberculosis potential of some ethnobotanically selected Malaysian plants," J Ethnopharmacol, vol. 133, pp. 1021-6, 2011.
  13. H. Noor and S. J. H. Ashcroft, "Pharmacological characterisation of the antihyperglycaemic properties of Tinospora crispa extract," Journal of Ethnopharmacology, vol. 62, pp. 7-13, 1998.
  14. C. T. Ruan, S. H. Lam, T. C. Chi, S. S. Lee, and M. J. Su, "Borapetoside C from Tinospora crispa improves insulin sensitivity in diabetic mice," Phytomedicine, vol. 19, pp. 719-24, 2012.
  15. A. R. N. Najib Nik, T. Furuta, S. Kojima, K. Takane, and M. Ali Mohd, "Antimalarial activity of extracts of Malaysian medicinal plants," J Ethnopharmacol, vol. 64, pp. 249-54, 1999.
  16. H. Kikuzaki, M. Hisamoto, K. Hirose, K. Akiyama, and H. Taniguchi, "Antioxidant properties of ferulic acid and its related compounds," J Agric Food Chem, vol. 50, pp. 2161-8, 2002.
  17. M. Ibrahim, W. Wan-Nor I’zzah, A. Narimah, Z. Nurul Asyikin, and S. Siti-Nur Shafinas, "Anti-proliperative and antioxidant effects of Tinospora crispa (Batawali)," Biomedical Research vol. 22, pp. 57-62, 2011.
  18. A. Mohd Nazri, M. S. Muhammad Ashraf, E. Zolkapli, H. H. Mizaton, H. Hamzah Fansuri, and W. I. Wan Iryani, "Anti-proliferative effect of Tinaspora crispa (L.) Hook. F. & Thompson and Gelam (Melaleuca sp.) honey on several cancer cell lines," in Business, Engineering and Industrial Applications (ISBEIA), 2011 IEEE Symposium on, 2011, pp. 545-548.
  19. S. Bogdanov, "Honey composition," Bee product science, pp. 1-13, 2009.
  20. A. M. Aljadi and M. Y. Kamaruddin, "Evaluation of the phenolic contents and antioxidant capacities of two Malaysian floral honeys," Food Chemistry, vol. 85, pp. 513-518, 2004.
  21. A. M. Aljadi and M. Y. Kamaruddin, "Isolation and Identification of Phenolic Acids in Malaysian Honey with Antibacterial Properties," Turk J Med Sci, vol. 33 pp. 229-236, 2002.
  22. C. T. Wen, S. Z. Hussein, S. Abdullah, N. A. Karim, S. Makpol, and Y. A. Mohd Yusof, "Gelam and Nenas honeys inhibit proliferation of HT 29 colon cancer cells by inducing DNA damage and apoptosis while suppressing inflammation," Asian Pac J Cancer Prev, vol. 13, pp. 1605-10, 2012.
  23. M. Kassim, M. Achoui, M. R. Mustafa, M. A. Mohd, and K. M. Yusoff, "Ellagic acid, phenolic acids, and flavonoids in Malaysian honey extracts demonstrate in vitro anti-inflammatory activity," Nutr Res, vol. 30, pp. 650-9, 2010.
  24. G. S. Hotamisligil, "Inflammatory pathways and insulin action," Int J Obes Relat Metab Disord, vol. 27, pp. S53-5, 2003.
  25. A. A. Azlim Almey, C. Ahmed Jalal Khan, I. Syed Zahir, K. Mustapha Suleiman, M. R. Aisyah, and K. Kamarul Rahim, "Total phenolic content and primary antioxidant activity of methanoloic and ethanolic extracts of aromatic plants' leaves," International Food Research Journal, vol. 17, pp. 1077-1084, 2010.
  26. N. D. Henry and P. A. Fair, "Comparison of in vitro cytotoxicity, estrogenicity and anti-estrogenicity of triclosan, perfluorooctane sulfonate and perfluorooctanoic acid," J Appl Toxicol, vol. 33, pp. 265-72, 2013.
  27. W. I. Ismail and T. S. Pillay, "Insulin resistance induced by antiretroviral drugs: Current understanding of molecular mechanisms," JEMDSA vol. 14, pp. 129-132, 2009.
  28. H. Chau, C. Mirtsos, and H. L. Huang, "Regulation of death complexes formation in tumor necrosis factor receptor signaling," Exp Cell Res, vol. 317, pp. 1841-50, 2011.
  29. National Institutes of Health US. (2004). ImageJ (Image Processing and Analysis in Java). Available: http://rsb.info.nih.gov/ij/
  30. A. E.-M. M. R. Afify, H. S. El-Beltagi, S. M. A. El-Salam, and A. A. Omran, "Biochemical changes in phenols, flavonoids, tannins, vitamin E, β–carotene and antioxidant activity during soaking of three white sorghum varieties," Asian Pacific Journal of Tropical Biomedicine, vol. 2, pp. 203-209, 2012.
  31. V. L. Singleton, R. Orthofer, and R. M. Lamuela-Raventós, "[14] Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent," in Methods in Enzymology. vol. Volume 299, P. Lester, Ed., ed: Academic Press, 1999, pp. 152-178.
  32. Promega, "Cell Titer 96 AQueous non-radioactive cell proliferation assay (MTS)," ed: Promega Pt Ltd, 2013.
  33. W. I. Ismail, J. A. King, K. Anwar, and T. S. Pillay, "Indinavir and nelfinavir inhibit proximal insulin receptor signalling and salicylate abrogates inhibition: Potential role of the NFkappa B pathway," J Cell Biochem, vol. 5, p. 24513, 2013.
  34. J. Yeh, J. Litz, P. Hauck, D. L. Ludwig, and G. W. Krystal, "Selective inhibition of SCLC growth by the A12 anti-IGF-1R monoclonal antibody correlates with inhibition of Akt," Lung Cancer, vol. 60, pp. 166-74, 2008.
  35. M. Nagase, T. Shiota, A. Tsushima, M. Murshedul Alam, S. Fukuoka, T. Yoshizawa, and N. Sakato, "Molecular mechanism of satratoxin-induced apoptosis in HL-60 cells: activation of caspase-8 and caspase-9 is involved in activation of caspase-3," Immunol Lett, vol. 84, pp. 23-7, 2002.
  36. S. B. Bratton, M. MacFarlane, K. Cain, and G. M. Cohen, "Protein complexes activate distinct caspase cascades in death receptor and stress-induced apoptosis," Exp Cell Res, vol. 256, pp. 27-33, 2000.