The Effect of 3-O-Acetyl-Beta-Boswellic Acid on Interleukin-6 Gene Expression in the Human Glioblastoma Cell Line

Document Type : Original Article (s)

Authors

1 PhD Candidate, Department of Biology, School of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran

2 Associate Professor, Department of Biology, School of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran

3 Professor, Department of Biology, School of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran

Abstract

Background: Frankincense is a gum resin of Boswellia trees genus that has been favored in the Iranian traditional medicine for its anti-inflammatory and anti-tumor properties. Glioblastoma is one of the most malignant adult cancers that is resistant to radiation therapy and chemotherapy. The aim of this study was to investigate the effect of an active ingredient of frankincense, 3-O-acetyl-beta-boswellic acid, on interleukin-6 expression in human glioblastoma cell line.Methods: Human glioblastoma cell line was obtained from cell bank of Pasteur Institute of Iran, and treated with different concentrations of 3-O-acetyl-beta-boswellic acid for 24 hours. The effect on cell survival was evaluated using MTT assay, and half maximal inhibitory concentration (IC50) was calculated as well. Cultured cells were treated with concentrations of 5, 15, and 25 μM of 3-O-acetyl-beta-boswellic acid. RNA was extracted and converted to complementary DNA (cDNA), and used for interleukin-6 expression studies via real-time polymerase chain reaction (PCR).Findings: IC50 was calculated as 39.88 μM. 3-O-acetyl-beta-boswellic acid at concentrations of 5, 15, and 25 μM significantly reduced the expression of interleukin-6 in a dose-dependent manner (P < 0.05).Conclusion: The results of this study indicate anti-inflammatory and anti-tumor effects of 3-O-acetyl-beta-boswellic acid by decreasing the expression of interleukin-6 in the inflammatory environment of glioblastoma tumor cells. Therefore, it can be considered as a beneficial ingredient in the treatment of glioblastoma.

Keywords

References

  1. Yeung YT, McDonald KL, Grewal T, Munoz L. Interleukins in glioblastoma pathophysiology: implications for therapy. Br J Pharmacol 2013; 168(3): 591-606.
  2. Paolillo M, Boselli C, Schinelli S. Glioblastoma under siege: An overview of current therapeutic strategies. Brain Sci 2018; 8(1): E15.
  3. Wang H, Lathia JD, Wu Q, Wang J, Li Z, Heddleston JM, et al. Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth. Stem Cells 2009; 27(10): 2393-404.
  4. Shan Y, He X, Song W, Han D, Niu J, Wang J. Role of IL-6 in the invasiveness and prognosis of glioma. Int J Clin Exp Med 2015; 8(6): 9114-20.
  5. Weissenberger J, Loeffler S, Kappeler A, Kopf M, Lukes A, Afanasieva TA, et al. IL-6 is required for glioma development in a mouse model. Oncogene 2004; 23(19): 3308-16.
  6. Liu Q, Li G, Li R, Shen J, He Q, Deng L, et al. IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines. J Neurooncol 2010; 100(2): 165-76.
  7. Zhang J, Sarkar S, Cua R, Zhou Y, Hader W, Yong VW. A dialog between glioma and microglia that promotes tumor invasiveness through the CCL2/CCR2/interleukin-6 axis. Carcinogenesis 2012; 33(2): 312-9.
  8. Michaud-Levesque J, Bousquet-Gagnon N, Beliveau R. Quercetin abrogates IL-6/STAT3 signaling and inhibits glioblastoma cell line growth and migration. Exp Cell Res 2012; 318(8): 925-35.
  9. Krohn K, Rao MS, Raman NV, Khalilullah M. High-performance thin layer chromatographic analysis of anti-inflammatory triterpenoids from Boswellia serrata Roxb. Phytochem Anal 2001; 12(6): 374-6.
  10. Liu JJ, Nilsson A, Oredsson S, Badmaev V, Zhao WZ, Duan RD. Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells. Carcinogenesis 2002; 23(12): 2087-93.
  11. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65(1-2): 55-63.
  12. Kitano H. Cancer as a robust system: Implications for anticancer therapy. Nat Rev Cancer 2004; 4(3): 227-35.
  13. Forouzandeh S, Naghsh N, Salimi S, Jahantigh D. Cytotoxic effect of boswellia serrata hydroalcholic extract on human cervical carcinoma epithelial cell line. Med Lab J 2014; 8(1): 7-13. [In Persian].
  14. Bhushan S, Kumar A, Malik F, Andotra SS, Sethi VK, Kaur IP, et al. A triterpenediol from Boswellia serrata induces apoptosis through both the intrinsic and extrinsic apoptotic pathways in human leukemia HL-60 cells. Apoptosis 2007; 12(10): 1911-26.
  15. Hoernlein RF, Orlikowsky T, Zehrer C, Niethammer D, Sailer ER, Simmet T, et al. Acetyl-11-keto-beta-boswellic acid induces apoptosis in HL-60 and CCRF-CEM cells and inhibits topoisomerase I. J Pharmacol Exp Ther 1999; 288(2): 613-9.
  16. Gandhi T, Gandhi K, Monapara K. Evaluation of Anti-cancer activity of Boswellic acid and Montelukast sodium against human prostate cancer cell line PC-3. Iran J Pharm Sci 2016; 12(4): 15-32. [In Persian].
  17. Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med 2018; 24(5): 541-50.
  18. Ohno Y, Toyoshima Y, Yurino H, Monma N, Xiang H, Sumida K, et al. Lack of interleukin-6 in the tumor microenvironment augments type-1 immunity and increases the efficacy of cancer immunotherapy. Cancer Sci 2017; 108(10): 1959-66.
  19. Han TJ, Cho BJ, Choi EJ, Kim DH, Song SH, Paek SH, et al. Inhibition of STAT3 enhances the radiosensitizing effect of temozolomide in glioblastoma cells in vitro and in vivo. J Neurooncol 2016; 130(1): 89-98.
Journal of Isfahan Medical School
Volume 37, Issue 516 - Serial Number 516
January and February 2019
Pages 125-131

Files

History

  • Receive Date: 12 February 2019
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics