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Immunomodulatory Effects of Hexane Insoluble Fraction of Ficus septica Burm. F. in Doxorubicin-treated Rats

  • Nugroho, Agung Endro (Cancer Chemoprevention Research Center) ;
  • Hermawan, Adam (Cancer Chemoprevention Research Center) ;
  • Nastiti, Kunti (Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada) ;
  • Suven, Suven (Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada) ;
  • Elisa, Pritha (Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada) ;
  • Hadibarata, Tony (Institute of Environmental and Water Resource Management, Universiti Teknologi) ;
  • Meiyanto, Edy (Cancer Chemoprevention Research Center)
  • Published : 2012.11.30

Abstract

The use of chemotherapeutics induces cardiotoxicity and affects immune functions, therefore development of combinatorial agents against cardiotoxicity and immunosuppression needs to be explored. Previous studies of the hexane insoluble fraction (HIF) of an ethanolic extract of Ficus septica leaves showed anticancer effects singly and in combination with doxorubicin on T47D breast cancer cells. In this present study, it was evaluated for its immunomodulatory activities in doxorubicin-treated rats. Thirty male Sprague Dawley rats were divided into five groups consisting of six rats each as follows: Group 1, receiving oral saline 10 ml/kg BW (control group); Group 2, receiving HIF dose 750 mg/kg BW orally, once daily; Group 3, receiving HIF dose 1.500 mg/kg BW orally, once daily; Group 4, given oral saline 10 ml/kg BW (normal group); Group 5, receiving HIF dose 1.500 mg/kg BW orally, once daily. The rats of group 1-3 were intramuscularly administered with doxorubicin at a dose of 4.67 mg/kg BW at the days 1 and 4 to suppress immune functions. Concomitantly, the rats were treated with saline or HIF for seven consecutive days (1 to 7). Treatment of HIF succeeded in reducing side effects of doxorubicin based on increasing lymphocyte density and phagocytosis activity and capacity of macrophages, as well as increasing the CD8+ blood level and decreasing spleen IL-10 expression. Hexane insoluble fraction of of ethanolic extract of Ficus septica leaves has potential as a protective agent combined with doxorubicin.

References

  1. Bokulić A, Garaj-Vrhovac V, Brajsa K, et al (2011). The effect of apigenin on cyclophosphamide and doxorubicin genotoxicity in vitro and in vivo. J Environ Sci Hlth A Tox Hazard Subst Environ Eng, 46, 526-33. https://doi.org/10.1080/10934529.2011.551744
  2. Bowles EJ, Wellman R, Feigelson HS, et al (2012). Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst, 104, 1293-305. https://doi.org/10.1093/jnci/djs317
  3. DeNardo DG, Andreu P, Coussens LM (2010). Interactions between lymphocytes and myeloid cells regulate pro-versus anti-tumor immunity. Cancer Metastasis Rev, 29, 309-16. https://doi.org/10.1007/s10555-010-9223-6
  4. Doster AR, Subramanian S, Yhee JY, et al (2010). Distribution and characterization of IL-10-secreting cells in lymphoid tissues of PCV2-infected pigs. J Vet Sci, 11, 177-83. https://doi.org/10.4142/jvs.2010.11.3.177
  5. Du G, Lin H, Yang Y, et al (2010). Dietary quercetin combining intratumoral doxorubicin injection synergistically induces rejection of established breast cancer in mice. Int Immunopharmacol, 10, 819-26. https://doi.org/10.1016/j.intimp.2010.04.018
  6. Emmerich J, Mumm JB, Chan IH, et al (2012). IL-10 directly activates and expands tumor-resident CD8(+) T cells without de novo infiltration from secondary lymphoid organs. Cancer Res, 72, 3570-81. https://doi.org/10.1158/0008-5472.CAN-12-0721
  7. Ferraro C, Quemeneur L, Prigent AF, et al (2000). Anthracyclines trigger apoptosis of both G0-G1 and cycling peripheral blood lymphocytes and induce massive deletion of mature T and B cells. Cancer Res, 60, 1901-7.
  8. Gotoh K, Inoue M, Masaki T, et al (2012). A novel antiinflammatory role for spleen-derived interleukin-10 in obesity-induced inflammation in white adipose tissue and liver. Diabetes, 61, 1994-2003. https://doi.org/10.2337/db11-1688
  9. Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell, 144, 646-74. https://doi.org/10.1016/j.cell.2011.02.013
  10. Min SY, Hwang SY, Park KS, et al (2004). Induction of IL-10-producing CD4+CD25+ T cells in animal model of collageninduced arthritis by oral administration of type II collagen. Arthritis Res Ther, 6, 213-9. https://doi.org/10.1186/ar1169
  11. Mubarok MF, Sekti DA, Ainun W (2008). Peningkatan Aktivitas Sitotoksik Doxorubicin terhadap Sel MCF-7 menggunakan Ekstrak Etanolik Daun Awar-awar (Ficus septic Burm. f.), Prosiding KONGRES ILMIAH XVI ISFI 2008. ISBN: 978-979-95107-6-2. Penerbit : Ikatan Sarjana Farmasi Indonesia (In Indonesian).
  12. Nugroho AE, Hermawan A, Putri DDP, et al (2012). Combinational Effects of Hexane Insoluble Fraction of Ficus septica Burm. F. and Doxorubicin Chemotherapy on T47D Breast Cancer Cells. Asian Pac J Tropical Biomedicine, In Press.
  13. Nugroho AE, Ikawati M, Hermawan, Putri DDP, et al (2011) Cytotoxic effect of ethanolic extract fractions of indonesia plant Ficus septica Burm. f. on human breast cancer T47D cell lines. Int J Phytomedicine, 3, 216-26.
  14. Panis C, Lemos GT, Victorino VJ, et al (2012). Immunological effects of taxol and adryamicin in breast cancer patients. Cancer Immunol Immunother, 61, 481-8. https://doi.org/10.1007/s00262-011-1117-0
  15. Pratama RH, Ikhtiarsyah YG, Anindyajati A, et al (2011). Awar-awar leaves ethanoric extract sinergistically enhances cytotoxic effect of doxorubicin on T47D breast cancer cells. Jurnal Ilmu Kefarmasian Indonesia, 9, 67-71.
  16. Pratten MK, Lloyd JB (1984). Phagocytic uptake of latex beads by rat peritoneal macrophages: comparison of morphological and radiochemical assay methods. Biosci Rep, 4, 497-504. https://doi.org/10.1007/BF01122225
  17. Rang HP, Dale MM, Ritter JM, et al (2003). Pharmacology. 5th Ed. Churchill Livingstone, Sydney;pp.693-698.
  18. Santos RVT, Caperuto EC, de Mello MT, et al (2010). Effect of doxorubicin on cytokine production by lymphocytes and the Th1/Th2 balance. Biomedicine & Pharmacotherapy, 64, 579-81. https://doi.org/10.1016/j.biopha.2010.02.002
  19. Saraiva M, O'Garra A. (2010). The regulation of IL-10 production by immune cells. Nat Rev Immunol, 10, 170-81. https://doi.org/10.1038/nri2711
  20. Sekti DA, Mubarok MF, Armandani I, et al (2010). Awar-Awar (Ficus Septica Burm. F.) Leaves Ethanolic Extract Induced Apoptosis of MCF-7 Cells By Downregulation of Bcl-2. J Trad Med, 15, 18-22.
  21. Shalhoub J, Falck-Hansen MA, Davies A, et al (2011). Innate immunity and monocyte-macrophage activation in atherosclerosis. J Inflammation, 8, 9-25. https://doi.org/10.1186/1476-9255-8-9
  22. Shibata N, Glass CK (2009). Regulation of macrophage function in inflammation and atherosclerosis. J Lipid Res, 50, 277-81. https://doi.org/10.1194/jlr.R800063-JLR200
  23. Tan ML, Choong PF, Dass CR (2009). Review: doxorubicin delivery systems based on chitosan for cancer therapy. J Pharm Pharmacol, 61, 131-42. https://doi.org/10.1211/jpp.61.02.0001
  24. Uspenskaya YA, Mikhutkina SV, Taksanova EI, et al (2004). Induction of apoptosis in bone marrow cells is mediated via purinergic receptors. Buletinof Experimental Biology and Med, 8, 116-9.
  25. WHO (2011). Cancer, World Health Organization, Switzerland. 2011. http://www.who.int/mediacentre/factsheet s/fs297/en/
  26. Wu PL, Rao KV, Su CH, et al (2002). Phenanthroindolizidine Alkaloids and Their Cytotoxicity from the Leaves of Ficus septica. Heterocycles, 57, 2401-8. https://doi.org/10.3987/COM-02-9615
  27. Yang Ci, Chen W, Wu PL, et al (2005). Anti-Inflammatory Mechanisms of Phenanthroindolizidine Alkaloid. Mol Pharmacol, 69, 749-58.
  28. Zhang XY, Li WG, Wu YJ, et al (2005a). Amelioration of doxorubicin-induced myocardial oxidative stress and immunosuppression by grape seed proanthocyanidins in tumour-bearing mice. J Pharm Pharmacol, 57, 1043-52. https://doi.org/10.1211/0022357056523
  29. Zhang XY, Li WG, Wu YJ, et al (2005b). Proanthocyanidin from grape seeds potentiates anti-tumor activity of doxorubicin via immunomodulatory mechanism. Int Immunopharmacol, 5, 1247-57. https://doi.org/10.1016/j.intimp.2005.03.004

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