Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Genistein Suppression of Matrix Metalloproteinase 2 (MMP-2) and Vascular Endothelial Growth Factor (VEGF) Expression in Mesenchymal Stem Cell Like Cells Isolated from High and Low Grade Gliomas

  • Yazdani, Yasaman (Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences) ;
  • Rad, Mohammad Reza Sharifi (Department of Neurosurgery, School of Medicine, Shiraz University of Medical Sciences) ;
  • Taghipour, Mousa (Department of Neurosurgery, School of Medicine, Shiraz University of Medical Sciences) ;
  • Chenari, Nooshafarin (Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences) ;
  • Ghaderi, Abbas (Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences) ;
  • Razmkhah, Mahboobeh (Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences)
  • Published : 2016.12.01
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Abstract

Objective: Brain tumors cause great mortality and morbidity worldwide, and success rates with surgical treatment remain very low. Several recent studies have focused on introduction of novel effective medical therapeutic approaches. Genistein is a member of the isoflavonoid family which has proved to exert anticancer effects. Here we assessed the effects of genistein on the expression of MMP-2 and VEGF in low and high grade gliomas in vitro. Materials and Methods: High and low grade glioma tumor tissue samples were obtained from a total of 16 patients, washed with PBS, cut into small pieces, digested with collagenase type I and cultured in DMEM containing 10% FBS. When cells reached passage 3, they were exposed to genistein and MMP-2 and VEGF gene transcripts were determined by quantitative real time PCR (qRT-PCR). Results: Expression of MMP-2 demonstrated 580-fold reduction in expression in low grade glioma cells post treatment with genistein compared to untreated cells (P value= 0.05). In cells derived from high grade lesions, expression of MMP-2 was 2-fold lower than in controls (P value> 0.05). Genistein caused a 4.7-fold reduction in VEGF transcript in high grade glioma cells (P value> 0.05) but no effects were evident in low grade glioma cells. Conclusion. Based on the data of the present study, low grade glioma cells appear much more sensitive to genistein and this isoflavone might offer an appropriate therapeutic intervention in these patients. Further investigation of this possibility is clearly warranted.

Keywords

Acknowledgement

Supported by : Shiraz University of Medical Sciences, Shiraz Institute for Cancer Research

References

  1. Abdullah JM, Mustafa Z, Ideris A (2014). Newcastle disease virus interaction in targeted therapy against proliferation and invasion pathways of glioblastoma multiforme. Biomed Res Int, 2014, 386470.
  2. Bourboulia D,Stetler-Stevenson WG (2010). Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion. Sem Cancer Biol, 20, 161-8. https://doi.org/10.1016/j.semcancer.2010.05.002
  3. Brewer GJ, LeRoux PD (2007). Human primary brain tumor cell growth inhibition in serum-free medium optimized for neuron survival. Brain Res, 1157,156-66. https://doi.org/10.1016/j.brainres.2007.04.064
  4. Brooks PC, Stromblad S, Sanders LC, et al (1996). Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin ${\alpha}v{\beta}3$. Cell, 85, 683-93. https://doi.org/10.1016/S0092-8674(00)81235-0
  5. Forsyth P, Wong H, Laing T, et al (1999). Gelatinase-A (MMP- 2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer, 79,1828. https://doi.org/10.1038/sj.bjc.6990291
  6. Gadgeel SM, Ali S, Philip PA, Wozniak A,Sarkar FH (2009). Genistein enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitors and inhibits nuclear factor kappa B in nonsmall cell lung cancer cell lines. Cancer, 115, 2165-76. https://doi.org/10.1002/cncr.24250
  7. Gomes FG, Nedel F, Alves AM, Nor JE,Tarquinio SBC (2013). Tumor angiogenesis and lymphangiogenesis: tumor/ endothelial crosstalk and cellular/microenvironmental signaling mechanisms. Life Sci, 92,101-7. https://doi.org/10.1016/j.lfs.2012.10.008
  8. Han L, Zhang H, Zhou W, Chen G, Guo K (2012). The effects of genistein on transforming growth factor-${\beta}1$-induced invasion and metastasis in human pancreatic cancer cell line Panc-1 in vitro. Chin Med J, 125, 2032-40.
  9. Khaw AK, Yong JWY, Kalthur G,Hande MP (2012). Genistein induces growth arrest and suppresses telomerase activity in brain tumor cells. Genes Chromosomes Cancer, 51,961-74. https://doi.org/10.1002/gcc.21979
  10. Le DM, Besson A, Fogg DK, et al (2003). Exploitation of astrocytes by glioma cells to facilitate invasiveness: a mechanism involving matrix metalloproteinase-2 and the urokinase-type plasminogen activator-plasmin cascade. J Neurosci, 23, 4034-43. https://doi.org/10.1523/JNEUROSCI.23-10-04034.2003
  11. Li Y, Sarkar FH (2002). Down-regulation of invasion and angiogenesis-related genes identified by cDNA microarray analysis of PC3 prostate cancer cells treated with genistein. Cancer Lett, 186, 157-64. https://doi.org/10.1016/S0304-3835(02)00349-X
  12. Maule F, Bresolin S, Rampazzo E, et al (2016). Annexin 2A sustains glioblastoma cell dissemination and proliferation. Oncotarget, 7, 54632. https://doi.org/10.18632/oncotarget.10565
  13. Munson J, Bonner M, Fried L, et al (2013). Identifying new small molecule anti-invasive compounds for glioma treatment. Cell Cycle, 12, 2200-9. https://doi.org/10.4161/cc.25334
  14. Myoung H, Hong SP, Yun PY, Lee JH, Kim MJ (2003). Anti-cancer effect of genistein in oral squamous cell carcinoma with respect to angiogenesis and in vitro invasion. Cancer Sci, 94, 215-20. https://doi.org/10.1111/j.1349-7006.2003.tb01422.x
  15. Nakahata AM, Suzuki DE, Rodini CO, et al (2010). Human glioblastoma cells display mesenchymal stem cell features and form intracranial tumors in immunocompetent rats. World J Stem Cells, 5,103-11.
  16. Nakamura H, Wang Y, Kurita T, et al (2011). Genistein increases epidermal growth factor receptor signaling and promotes tumor progression in advanced human prostate cancer. PloS One, 6, e20034. https://doi.org/10.1371/journal.pone.0020034
  17. Nakamura Y, Yogosawa S, Izutani Y, et al (2009). A combination of indole-3-carbinol and genistein synergistically induces apoptosis in human colon cancer HT-29 cells by inhibiting Akt phosphorylation and progression of autophagy. Mol Cancer, 8,1.
  18. Plaisier CL, O'Brien S, Bernard B, et al (2016). Causal mechanistic regulatory network for glioblastoma deciphered using systems genetics network analysis. Cell Systems, 3, 172-86. https://doi.org/10.1016/j.cels.2016.06.006
  19. Puli S, Lai JC, Bhushan A (2006). Inhibition of matrix degrading enzymes and invasion in human glioblastoma (U87MG) cells by isoflavones. J Neurooncol, 79, 135-42. https://doi.org/10.1007/s11060-006-9126-0
  20. Razmkhah M, Arabpour F, Taghipour M, et al (2013). Expression of chemokines and chemokine receptors in brain tumor tissue derived cells. Asian Pac J Cancer Prev, 15, 7201-5.
  21. Russo M, Russo GL, Daglia M, et al (2016). Understanding genistein in cancer: The “good” and the “bad” effects: A review. Food Chem, 196, 589-600. https://doi.org/10.1016/j.foodchem.2015.09.085
  22. Shao Z-M, Wu J, Shen Z-Z, Barsky SH (1998). Genistein exerts multiple suppressive effects on human breast carcinoma cells. Cancer Res, 58,4851-7.
  23. Shu XO, Zheng Y, Cai H, et al (2009). Soy food intake and breast cancer survival. JAMA, 302, 2437-43. https://doi.org/10.1001/jama.2009.1783
  24. Spagnuolo C, Russo GL, Orhan IE, et al (2015). Genistein and cancer: current status, challenges, and future directions. Advances in Nutrition. ADV NUTR, 6, 408-19. https://doi.org/10.3945/an.114.008052
  25. Stupp R, Mason WP, Van Den Bent MJ, et al (2005). Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med, 352, 987-96. https://doi.org/10.1056/NEJMoa043330
  26. Su S-J, Yeh T-M, Chuang W-J, et al (2005). The novel targets for anti-angiogenesis of genistein on human cancer cells. Biochem Pharmacol, 69, 307-18. https://doi.org/10.1016/j.bcp.2004.09.025
  27. Weber GF, Bjerke MA, DeSimone DW (2011). Integrins and cadherins join forces to form adhesive networks. J Cell Sci, 124, 1183-93. https://doi.org/10.1242/jcs.064618
  28. Weinstein IB (2002). Addiction to oncogenes-the Achilles heal of cancer. Science, 297, 63-4. https://doi.org/10.1126/science.1073096
  29. Yu X, Zhu J, Mi M, et al (2012). Anti-angiogenic genistein inhibits VEGF-induced endothelial cell activation by decreasing PTK activity and MAPK activation. Med Oncol, 29, 349-57. https://doi.org/10.1007/s12032-010-9770-2