DOI QR코드

DOI QR Code

5-Aminoisoquinolinone Reduces the Expression of Vascular Endothelial Growth Factor-C via the Nuclear Factor-kappa B Signaling Pathway in CT26 Cells

  • Wu, Wei-Qiang (Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University) ;
  • Fauzee, Nilufer Jasmine Selimah (Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University) ;
  • Wang, Ya-Lan (Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University)
  • Published : 2012.03.31

Abstract

Objective: VEGF-C has recently been identified as a key molecule which is involved in tumor lymphangiogenesis. The aim of this research was to investigate the role of PARP-1 inhibition in the regulation of VEGF-C expression in CT26 cells. Methods: CT26 cells were treated with or without the PARP-1 inhibitor 5-aminoisoquinolinone (5-AIQ). The expression of PARP-1, NF-kB, and VEGF-C proteins in CT26 cells was measured by Western blot analysis and the VEGF-C mRNA level was determined by reverse transcription polymerase chain reaction (RT-PCR). CT26-secreted VEGF-C was detected by enzyme-linked immunosorbent assay (ELISA). Results: The results of Western blot analysis showed that the expression levels of PARP-1, NF-kB, and VEGF-C were reduced in 5-AIQ treated CT26 cells and the levels of VEGF-C mRNA in 5-AIQ treated CT26 were significantly lower than t in 5-AIQ-untreated cells (P<0.05). The concentrations of CT26-secreted VEGF-C were also dramatically decreased (P<0.05). Conclusion: Here, we provide evidence for the first time that PARP-1 inhibition dramatically reduces VEGF-C expression via the nuclear factor NF-kB signaling pathway. We therefore propose that PARP-1 inhibition has an anti-lymphangiogenic effect and may contribute to the prevention of metastatic dissemination via the lymphatic system.

Keywords

References

  1. Chen Z, Varney ML, Backora MW, et al (2005). Downregulation of vascular endothelial cell growth factor-C expression using small interfering RNA vectors in mammary tumors inhibits tumor lymphangiogenesis and spontaneous metastasis and enhances survival. Cancer Res, 65, 9004-11. https://doi.org/10.1158/0008-5472.CAN-05-0885
  2. Chilov D, Kukk E, Taira S, et al (1997). Genomic organization of human and mouse genes for vascular endothelial growth factor C. J Biol Chem, 272, 25176-83. https://doi.org/10.1074/jbc.272.40.25176
  3. Cuzzocrea S, Mazzon E, Di Paola R, et al (2004). 5-Aminoisoquinolinone reduces colon injury by experimental colitis. Naunyn Schmiedebergs Arch Pharmacol, 370, 464- 73. https://doi.org/10.1007/s00210-004-1002-x
  4. Diefenbach J, Bürkle A (2005). Introduction to poly (ADPribose) metabolism. Cell Mol Life Sci, 62, 721-30. https://doi.org/10.1007/s00018-004-4503-3
  5. Di Paola R, Mazzon E, Muia C, et al (2007). 5-Aminoisoquinolin- 1(2H)-one, a water-soluble poly (ADP-ribose) polymerase (PARP) inhibitor reduces the evolution of experimental periodontitis in rats. J Clin Periodontol, 34, 95-102. https://doi.org/10.1111/j.1600-051X.2006.01016.x
  6. Fauzee NJS, Pan J, Wang YL (2010). PARP and PARG inhibitorsnew therapeutic targets in cancer treatment. Pathol Oncol Res, 16, 469-78 https://doi.org/10.1007/s12253-010-9266-6
  7. Fauzee NJS, Qiaozhuan L, Wang YL, et al (2012). silencing poly (ADP-Ribose) glycohydrolase (PARG) expression inhibits growth of human colon cancer cells in vitro via PI3K/Akt/ $NF_{\kappa}-B$ pathway. Pathol Oncol Res, 18, 191-9. https://doi.org/10.1007/s12253-011-9428-1
  8. Hassa PO, Haenni SS, Buerki C, et al (2005). Acetylation of poly (ADP-ribose) polymerase-1 by p300/CREB-binding protein regulates coactivation of NF-kappaB-dependent transcription. J Biol Chem, 280, 40450-64. https://doi.org/10.1074/jbc.M507553200
  9. He XW, Liu T, Xiao Y, et al (2009). Vascular endothelial growth factor-C siRNA delivered via calcium carbonate nanoparticle effectively inhibits lymphangiogenesis and growth of colorectal cancer in vivo. Cancer Biother Radiopharm, 24, 249-59. https://doi.org/10.1089/cbr.2008.0515
  10. He Y, Rajantie I, Pajusola K, et al (2005). Vascular endothelial cell growth factor receptor 3-mediated activation of lymphatic endothelium is crucial for tumor cell entry and spread via lymphatic vessels. Cancer Res, 65, 4739-46. https://doi.org/10.1158/0008-5472.CAN-04-4576
  11. Hsieh CY, Chen CA, Chou CH, et al (2004). Overexpression of Her-2/NEU in epithelial ovarian carcinoma induces vascular endothelial growth factor C by activating NF-kappa B: implications for malignant ascites formation and tumor lymphangiogenesis. J Biomed Sci, 11, 249-59.
  12. Isabelle M, Moreel X, Gagné JP et al (2010) Investigation of PARP-1, PARP-2, and PARG interactomes by affinitypurification mass spectrometry. Proteome Sci, 8, 22. https://doi.org/10.1186/1477-5956-8-22
  13. Karpanen T, Egeblad M, Karkkainen MJ, et al (2001). Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res, 61, 1786-90.
  14. Lee HK, Lee JH, Kim M, et al (2006). Insulin-like growth factor-1 induces migration and expression of laminin-5 in cultured human corneal epithelial cell. Invest Ophthalmol Vis Sci, 47, 873-82. https://doi.org/10.1167/iovs.05-0826
  15. Li M, Threadgill MD, Wang Y, et al (2009). Poly (ADP-ribose) polymerase inhibition down-regulates expression of metastasis-related genes in CT26 colon carcinoma cells. Pathobiology, 76, 108-16. https://doi.org/10.1159/000209388
  16. Li Q, Li M, Wang YL, et al (2012). RNA interference of PARG could inhibit the metastatic potency of colon carcinoma cells via PI3-Kinase/Akt pathway. Cellular Physiol Biochem, 29, 361-72. https://doi.org/10.1159/000338491
  17. Lin J, Lalani AS, Harding TC, et al (2005). Inhibition of lymphogenous metastasis using adeno-associated virusmediated gene transfer of a soluble VEGFR-3 decoy receptor. Cancer Res, 65, 6901-9. https://doi.org/10.1158/0008-5472.CAN-05-0408
  18. Mandriota SJ, Jussila L, Jeltsch M, et al (2001). Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J, 20, 672-82. https://doi.org/10.1093/emboj/20.4.672
  19. Palfi A, Toth A, Kulcsar G, et al (2005). The role of akt and mitogen-activated protein kinase systems in the protective effect of poly (ADP-Ribose) polymerase inhibition in langendorff perfused and inisoproterenol-damaged rat hearts. J Pharmacol Exp Ther, 315, 273-82. https://doi.org/10.1124/jpet.105.088336
  20. Petrilli V, Herceg Z, Hassa PO, et al (2004). Noncleavable poly (ADP-ribose) polymerase-1 regulates the inflammation response in mice. J Clin Invest, 114, 1072-81. https://doi.org/10.1172/JCI200421854
  21. Rajesh M, Mukhopadhyay P, Godlewski G, et al (2006). Poly (ADP-ribose) polymerase inhibition decreases angiogenesis. Biochem Biophys Res Commun, 350, 1056-62. https://doi.org/10.1016/j.bbrc.2006.09.160
  22. Renyi-Vamos F, Tovari J, Fillinger J, et al (2005). Lymphangiogenesis correlates with lymph node metastasis, progno-sis, and angiogenic phenotype in human non-small cell lung cancer. Clin Cancer Res, 11, 7344-53. https://doi.org/10.1158/1078-0432.CCR-05-1077
  23. Roberts N, Kloos B, Cassella M, et al (2006). Inhibition of VEGFR-3 activation with the antagonistic antibody more potently suppresses lymph node and distant metastases than inactivation of VEGFR-2. Cancer Res, 66, 2650-7. https://doi.org/10.1158/0008-5472.CAN-05-1843
  24. Rothwarf DM, Karin M (1999). The NF-kB activation pathway: a paradigm in information transfer from membrane to nucleus. Sci STKE, 5, RE1.
  25. Skobe M, Hawighorst T, Jackson DG, et al (2001). Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med, 7, 192-8. https://doi.org/10.1038/84643
  26. Sun P, Gao J, Liu YL, et al (2008). RNA interference (RNAi)- mediated vascular endothelial growth factor-C (VEGF-C) reduction interferes with lymphangiogenesis and enhances epirubicin sensitivity of breast cancer cells. Mol Cell Biochem, 308, 161-8. https://doi.org/10.1007/s11010-007-9624-1
  27. Tsai PW, Shiah SG, Lin MT, et al (2003). Up-regulation of vascular endothelial growth factor C in breast cancer cells by heregulin-beta 1. A critical role of p38/nuclear factor-kappa B signaling pathway. J Biol Chem, 278, 5750-9. https://doi.org/10.1074/jbc.M204863200
  28. Watari K, Nakao S, Fotovati A, et al (2008). Role of macrophages in inflammatory lymphangiogenesis: Enhanced production of vascular endothelial growth factor C and D through NFkappaB activation. Biochem Biophys Res Commun, 377, 826-31. https://doi.org/10.1016/j.bbrc.2008.10.077
  29. Woon ECY, Threadgill MD (2005). Poly (ADP-ribose) polymerase inhibition-where now? Curr Med Chem, 12, 2373-92. https://doi.org/10.2174/0929867054864778
  30. Zhang D, Li B, Shi J, et al (2010). Suppression of tumor growth and metastasis by simultaneously blocking vascular endothelial growth factor (VEGF)-A and VEGF-C with a receptor-immunoglobulin fusion protein. Cancer Res, 70, 2495-503. https://doi.org/10.1158/0008-5472.CAN-09-3488
  31. Zhang Q, Lu Y, Proulx ST, et al (2007). Increased lymphangiogenesis in joints of mice with inflammatory arthritis. Arthritis Res Ther, 9, R118. https://doi.org/10.1186/ar2326
  32. Zheng L, Szabo C, Kern TS (2004). Poly (ADP-ribose) polymerase is involved in the development of diabetic retinopathy via regulation of nuclear factor-kappaB. Diabetes, 53, 2960-7. https://doi.org/10.2337/diabetes.53.11.2960

Cited by

  1. High Mobility Group Box-1 Promotes Inflammation-Induced Lymphangiogenesis via Toll-Like Receptor 4-Dependent Signalling Pathway vol.11, pp.4, 2016, https://doi.org/10.1371/journal.pone.0154187