Advertisement

Potential molecular mechanisms underlying the effect of arsenic on angiogenesis

  • Juan Zhang
  • Yue Zhang
  • Weiyan Wang
  • Zhiyi ZhangEmail author
Review
  • 31 Downloads

Abstract

Arsenic is a potent chemotherapeutic drug that is applied as a treatment for cancer; it exerts its functions through multiple pathways, including angiogenesis inhibition. As angiogenesis is a critical component of the progression of many diseases, arsenic is a feasible treatment option for patients with other angiogenic diseases, including rheumatoid arthritis and psoriasis, among others. However, arsenic is also a well-known carcinogen, demonstrating a pro-angiogenesis effect. This review will focus on the dual effects of arsenic on neovascularization and the relevant mechanisms underlying these effects, aiming to provide a rational understanding of arsenic treatment. In particular, we expect to provide a comprehensive overview of the current knowledge of the mechanisms by which arsenic influences angiogenesis.

Keywords

Arsenic trioxide Arsenite Cancer Angiogenesis Toxicity 

Notes

Acknowledgements

This work is supported by National Natural Science Foundation of China (NSFC 81771749) to Zhiyi Zhang, Chinese Postdoctoral Science Foundation (Grant No. 2019M651309) to Juan Zhang, Heilongjiang Provincial Postdoctoral Science Foundation (Grant No. LBH-Z18226) to Juan Zhang, and Scientific Research Innovation Foundation of the First Affiliated Hospital of Harbin Medical University (Grant No. 2019B18) to Juan Zhang.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

References

  1. Antonelli R, Shao K, Thomas DJ, Sams R 2nd, Cowden J (2014) AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility. Environ Res 132:156–167.  https://doi.org/10.1016/j.envres.2014.03.012 CrossRefPubMedGoogle Scholar
  2. Arroyo AG, Iruela-Arispe ML (2010) Extracellular matrix, inflammation, and the angiogenic response. Cardiovasc Res 86:226–235.  https://doi.org/10.1093/cvr/cvq049 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Augustin HG, Koh GY, Thurston G, Alitalo K (2009) Control of vascular morphogenesis and homeostasis through the angiopoietin-tie system. Nat Rev Mol Cell Biol 10:165–177.  https://doi.org/10.1038/nrm2639 CrossRefPubMedGoogle Scholar
  4. Basu P, Ghosh RN, Grove LE, Klei L, Barchowsky A (2008) Angiogenic potential of 3-nitro-4-hydroxy benzene arsonic acid (roxarsone). Environ Health Perspect 116:520–523.  https://doi.org/10.1289/ehp.10885 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bellamy WT, Richter L, Frutiger Y, Grogan TM (1999) Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. Cancer Res 59:728–733PubMedGoogle Scholar
  6. Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307.  https://doi.org/10.1038/nature10144 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Chun YS, Kim MS, Park JW (2002) Oxygen-dependent and -independent regulation of HIF-1alpha. J Korean Med Sci 17:581–588.  https://doi.org/10.3346/jkms.2002.17.5.581 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Chung I, Han G, Seshadri M, Gillard BM, Yu WD (2009) Role of vitamin D receptor in the antiproliferative effects of calcitriol in tumor-derived endothelial cells and tumor angiogenesis in vivo. Cancer Res 69:967–975.  https://doi.org/10.1158/0008-5472.CAN-08-2307 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Covello KL, Simon MC (2004) HIFs, hypoxia, and vascular development. Curr Top Dev Biol 62:37–54.  https://doi.org/10.1016/S0070-2153(04)62002-3 CrossRefPubMedGoogle Scholar
  10. De Palma M, Biziato D, Petrova TV (2017) Microenvironmental regulation of tumour angiogenesis. Nat Rev Cancer 17:457–474.  https://doi.org/10.1038/nrc.2017.51 CrossRefPubMedGoogle Scholar
  11. de The H, Chen Z (2010) Acute promyelocytic leukaemia: novel insights into the mechanisms of cure. Nat Rev Cancer 10:775–783.  https://doi.org/10.1038/nrc2943 CrossRefPubMedGoogle Scholar
  12. Duxbury JM, Mayer AB, Lauren JG, Hassan N (2003) Food chain aspects of arsenic contamination in Bangladesh: effects on quality and productivity of rice. J Environ Sci Health A 38:61–69.  https://doi.org/10.1081/ESE-120016881 CrossRefGoogle Scholar
  13. Duyndam MC, Hulscher TM, Fontijn D, Pinedo HM, Boven E (2001) Induction of vascular endothelial growth factor expression and hypoxia-inducible factor 1alpha protein by the oxidative stressor arsenite. J Biol Chem 276:48066–48076.  https://doi.org/10.1074/jbc.M106282200 CrossRefPubMedGoogle Scholar
  14. Duyndam MC, Hulscher ST, van der Wall E, Pinedo HM, Boven E (2003) Evidence for a role of p38 kinase in hypoxia-inducible factor 1-independent induction of vascular endothelial growth factor expression by sodium arsenite. J Biol Chem 278:6885–6895.  https://doi.org/10.1074/jbc.M206320200 CrossRefPubMedGoogle Scholar
  15. Eilken HM, Adams RH (2010) Dynamics of endothelial cell behavior in sprouting angiogenesis. Curr Opin Cell Biol 22:617–625.  https://doi.org/10.1016/j.ceb.2010.08.010 CrossRefPubMedGoogle Scholar
  16. Fiedler W, Graeven U, Ergun S, Verago S, Kilic N (1997) Vascular endothelial growth factor, a possible paracrine growth factor in human acute myeloid leukemia. Blood 89:1870–1875CrossRefGoogle Scholar
  17. Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF (2008) miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 15:272–284.  https://doi.org/10.1016/j.devcel.2008.07.008 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Folkman J (2007) Is angiogenesis an organizing principle in biology and medicine? J Pediatr Surg 42:1–11.  https://doi.org/10.1016/j.jpedsurg.2006.09.048 CrossRefPubMedGoogle Scholar
  19. Gao JK, Wang LX, Long B, Ye XT, Su JN (2015) Arsenic trioxide inhibits cell growth and invasion via down-regulation of Skp2 in pancreatic cancer cells. Asian Pac J Cancer Prev 16:3805–3810.  https://doi.org/10.7314/APJCP.2015.16.9.3805 CrossRefPubMedGoogle Scholar
  20. Ge HY, Han ZJ, Tian P, Sun WJ, Xue DX (2015) VEGFA expression is inhibited by arsenic trioxide in HUVECs through the upregulation of Ets-2 and miRNA-126. PLoS ONE 10:e0135795.  https://doi.org/10.1371/journal.pone.0135795 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Goel S, Duda DG, Xu L, Munn LL, Boucher Y (2011) Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev 91:1071–1121.  https://doi.org/10.1152/physrev.00038.2010 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Harris TA, Yamakuchi M, Kondo M, Oettgen P, Lowenstein CJ (2010) Ets-1 and Ets-2 regulate the expression of microRNA-126 in endothelial cells. Arterioscler Thromb Vasc Biol 30:1990–1997.  https://doi.org/10.1161/ATVBAHA.110.211706 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Hei TK, Filipic M (2004) Role of oxidative damage in the genotoxicity of arsenic. Free Radic Biol Med 37:574–581.  https://doi.org/10.1016/j.freeradbiomed.2004.02.003 CrossRefPubMedGoogle Scholar
  24. Hirano S, Kobayashi Y, Cui X, Kanno S, Hayakawa T, Shraim A (2004) The accumulation and toxicity of methylated arsenicals in endothelial cells: important roles of thiol compounds. Toxicol Appl Pharmacol 198:458–467.  https://doi.org/10.1016/j.taap.2003.10.023 CrossRefPubMedGoogle Scholar
  25. Huang H, Bhat A, Woodnutt G, Lappe R (2010) Targeting the ANGPT-TIE2 pathway in malignancy. Nat Rev Cancer 10:575–585.  https://doi.org/10.1038/nrc2894 CrossRefPubMedGoogle Scholar
  26. Huang L, Wu H, van der Kuijp TJ (2015) The health effects of exposure to arsenic-contaminated drinking water: a review by global geographical distribution. Int J Environ Health Res 25:432–452.  https://doi.org/10.1080/09603123.2014.958139 CrossRefPubMedGoogle Scholar
  27. Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62.  https://doi.org/10.1126/science.1104819 CrossRefGoogle Scholar
  28. Ji H, Li Y, Jiang F, Wang X, Zhang J (2014) Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer. Cancer Sci 105:1541–1549.  https://doi.org/10.1111/cas.12548 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Jiang F, Wang X, Liu Q, Shen J, Li Z (2014) Inhibition of TGF-beta/SMAD3/NF-kappaB signaling by microRNA-491 is involved in arsenic trioxide-induced anti-angiogenesis in hepatocellular carcinoma cells. Toxicol Lett 231:55–61.  https://doi.org/10.1016/j.toxlet.2014.08.024 CrossRefPubMedGoogle Scholar
  30. Jiang F, Li Y, Si L, Zhang Z, Li Z (2019) Interaction of EZH2 and P65 is involved in the arsenic trioxide-induced anti-angiogenesis in human triple-negative breast cancer cells. Cell Biol Toxicol.  https://doi.org/10.1007/s10565-018-09458-0 CrossRefPubMedGoogle Scholar
  31. Kamat CD, Green DE, Curilla S, Warnke L, Hamilton JW (2005) Role of HIF signaling on tumorigenesis in response to chronic low-dose arsenic administration. Toxicol Sci 86:248–257.  https://doi.org/10.1093/toxsci/kfi190 CrossRefPubMedGoogle Scholar
  32. Kao YH, Yu CL, Chang LW, Yu HS (2003) Low concentrations of arsenic induce vascular endothelial growth factor and nitric oxide release and stimulate angiogenesis in vitro. Chem Res Toxicol 16:460–468.  https://doi.org/10.1021/tx025652a CrossRefPubMedGoogle Scholar
  33. Karateev DE (2003) Angiogenesis in rheumatoid arthritis. Vestn Ross Akad Med Nauk.  https://doi.org/10.2741/1657 CrossRefPubMedGoogle Scholar
  34. Khairul I, Wang QQ, Jiang YH, Wang C, Naranmandura H (2017) Metabolism, toxicity and anticancer activities of arsenic compounds. Oncotarget 8:23905–23926.  https://doi.org/10.18632/oncotarget.14733 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Klei LR, Barchowsky A (2008) Positive signaling interactions between arsenic and ethanol for angiogenic gene induction in human microvascular endothelial cells. Toxicol Sci 102:319–327.  https://doi.org/10.1093/toxsci/kfn003 CrossRefPubMedGoogle Scholar
  36. Kobayashi Y, Hayakawa T, Hirano S (2007) Expression and activity of arsenic methyltransferase Cyt19 in rat tissues. Environ Toxicol Pharmacol 23:115–120.  https://doi.org/10.1016/j.etap.2006.07.010 CrossRefPubMedGoogle Scholar
  37. Korc M, Friesel RE (2009) The role of fibroblast growth factors in tumor growth. Curr Cancer Drug Targets 9:639–651.  https://doi.org/10.2174/156800909789057006 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Kumagai Y, Pi J (2004) Molecular basis for arsenic-induced alteration in nitric oxide production and oxidative stress: implication of endothelial dysfunction. Toxicol Appl Pharmacol 198:450–457.  https://doi.org/10.1016/j.taap.2003.10.031 CrossRefPubMedGoogle Scholar
  39. Lew YS, Brown SL, Griffin RJ, Song CW, Kim JH (1999) Arsenic trioxide causes selective necrosis in solid murine tumors by vascular shutdown. Cancer Res 59:6033–6037PubMedGoogle Scholar
  40. Li HM, Long Y, Qing C, Yu M, Li ZH (2011) Arsenic trioxide induces apoptosis of Burkitt lymphoma cell lines through multiple apoptotic pathways and triggers antiangiogenesis. Oncol Res 19:149–163.  https://doi.org/10.3727/096504011X12935427587885 CrossRefPubMedGoogle Scholar
  41. Li C, Qu X, Xu W, Qu N, Mei L (2013) Arsenic trioxide induces cardiac fibroblast apoptosis in vitro and in vivo by up-regulating TGF-beta1 expression. Toxicol Lett 219:223–230.  https://doi.org/10.1016/j.toxlet.2013.03.024 CrossRefPubMedGoogle Scholar
  42. Li C, Zhang J, Wang W, Wang H, Zhang Y, Zhang Z (2019) Arsenic trioxide improves Treg and Th17 balance by modulating STAT3 in treatment-naive rheumatoid arthritis patients. Int Immunopharmacol 73:539–551.  https://doi.org/10.1016/j.intimp.2019.05.001 CrossRefPubMedGoogle Scholar
  43. Liu B, Pan S, Dong X, Qiao H, Jiang H (2006) Opposing effects of arsenic trioxide on hepatocellular carcinomas in mice. Cancer Sci 97:675–681.  https://doi.org/10.1111/j.1349-7006.2006.00230.x CrossRefPubMedGoogle Scholar
  44. Liu H, Zhang Z, Chi X, Zhao Z, Huang D (2016) Arsenite-loaded nanoparticles inhibit PARP-1 to overcome multidrug resistance in hepatocellular carcinoma cells. Sci Rep 6:31009.  https://doi.org/10.1038/srep31009 CrossRefPubMedPubMedCentralGoogle Scholar
  45. Lohela M, Bry M, Tammela T, Alitalo K (2009) VEGFs and receptors involved in angiogenesis versus lymphangiogenesis. Curr Opin Cell Biol 21:154–165.  https://doi.org/10.1016/j.ceb.2008.12.012 CrossRefPubMedGoogle Scholar
  46. Luo D, Zhang X, Du R, Gao W, Luo N (2018) Low dosage of arsenic trioxide (As2O3) inhibits angiogenesis in epithelial ovarian cancer without cell apoptosis. J Biol Inorg Chem 23:939–947.  https://doi.org/10.1007/s00775-018-1595-z CrossRefPubMedGoogle Scholar
  47. Meharg AA, Rahman MM (2003) Arsenic contamination of Bangladesh paddy field soils: implications for rice contribution to arsenic consumption. Environ Sci Technol 37:229–234.  https://doi.org/10.1021/es0259842 CrossRefPubMedGoogle Scholar
  48. Meng D, Wang X, Chang Q, Hitron A, Zhang Z, Xu M, Chen G, Luo J, Jiang B, Fang J, Shi X (2010) Arsenic promotes angiogenesis in vitro via a heme oxygenase-1-dependent mechanism. Toxicol Appl Pharmacol 244:291–299.  https://doi.org/10.1016/j.taap.2010.01.004 CrossRefPubMedGoogle Scholar
  49. Mohammadi Kian M, Mohammadi S, Tavallaei M, Chahardouli B, Rostami S (2018) Inhibitory effects of arsenic trioxide and thalidomide on angiogenesis and vascular endothelial growth factor expression in leukemia cells. Asian Pac J Cancer Prev 19:1127–1134.  https://doi.org/10.22034/APJCP.2018.19.4.1127 CrossRefPubMedGoogle Scholar
  50. Mousa SA, O’Connor L, Rossman TG, Block E (2007) Pro-angiogenesis action of arsenic and its reversal by selenium-derived compounds. Carcinogenesis 28:962–967CrossRefGoogle Scholar
  51. Onimaru M, Yonemitsu Y (2011) Angiogenic and lymphangiogenic cascades in the tumor microenvironment. Front Biosci 3:216–225.  https://doi.org/10.1093/carcin/bgl229 CrossRefGoogle Scholar
  52. Papapetropoulos A, Garcia-Cardena G, Madri JA, Sessa WC (1997) Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 100:3131–3139.  https://doi.org/10.1172/JCI119868 CrossRefPubMedPubMedCentralGoogle Scholar
  53. Phng LK, Potente M, Leslie JD, Babbage J, Nyqvist D (2009) Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density in angiogenesis. Dev Cell 16:70–82.  https://doi.org/10.1016/j.devcel.2008.12.009 CrossRefPubMedGoogle Scholar
  54. Potente M, Gerhardt H, Carmeliet P (2011) Basic and therapeutic aspects of angiogenesis. Cell 146:873–887.  https://doi.org/10.1016/j.cell.2011.08.039 CrossRefPubMedGoogle Scholar
  55. Qu H, Tong D, Zhang Y, Kang K, Zhang Y (2013) The synergistic antitumor activity of arsenic trioxide and vitamin K2 in HL-60 cells involves increased ROS generation and regulation of the ROS-dependent MAPK signaling pathway. Pharmazie 68:839–845PubMedGoogle Scholar
  56. Rafii S, Butler JM, Ding BS (2016) Angiocrine functions of organ-specific endothelial cells. Nature 529:316–325.  https://doi.org/10.1038/nature17040 CrossRefPubMedPubMedCentralGoogle Scholar
  57. Roboz GJ, Dias S, Lam G, Lane WJ, Soignet SL (2000) Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis. Blood 96:1525–1530.  https://doi.org/10.1016/S1246-7820(00)80033-6 CrossRefPubMedGoogle Scholar
  58. Saint-Jacques N, Parker L, Brown P, Dummer TJ (2014) Arsenic in drinking water and urinary tract cancers: a systematic review of 30 years of epidemiological evidence. Environ Health 13:44.  https://doi.org/10.1186/1476-069X-13-44 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Shankar S, Shanker U (2014) Arsenic contamination of groundwater: a review of sources, prevalence, health risks, and strategies for mitigation. Sci World J 2014:304524.  https://doi.org/10.1155/2014/304524 CrossRefGoogle Scholar
  60. Shen ZY, Shen J, Chen MH, Wu XY, Wu MH, Zeng Y (2003) The inhibition of growth and angiogenesis in heterotransplanted esophageal carcinoma via intratumoral injection of arsenic trioxide. Oncol Rep 10:1869–1874.  https://doi.org/10.3892/or.10.6.1869 CrossRefPubMedGoogle Scholar
  61. Singh R, Singh S, Parihar P, Singh VP, Prasad SM (2015) Arsenic contamination, consequences and remediation techniques: a review. Ecotoxicol Environ Saf 112:247–270.  https://doi.org/10.1016/j.ecoenv.2014.10.009 CrossRefPubMedGoogle Scholar
  62. Soucy NV, Ihnat MA, Kamat CD, Hess L, Post MJ (2003) Arsenic stimulates angiogenesis and tumorigenesis in vivo. Toxicol Sci 76:271–279.  https://doi.org/10.1093/toxsci/kfg231 CrossRefPubMedGoogle Scholar
  63. States JC, Srivastava S, Chen Y, Barchowsky A (2009) Arsenic and cardiovascular disease. Toxicol Sci 107:312–323.  https://doi.org/10.1093/toxsci/kfn236 CrossRefPubMedGoogle Scholar
  64. Straub AC, Klei LR, Stolz DB, Barchowsky A (2009) Arsenic requires sphingosine-1-phosphate type 1 receptors to induce angiogenic genes and endothelial cell remodeling. Am J Pathol 174:1949–1958.  https://doi.org/10.2353/ajpath.2009.081016 CrossRefPubMedPubMedCentralGoogle Scholar
  65. Sun H, Ma L, Hu Z (1992) Arsenic trioxide treated 32 cases of acute promyelocytic leukemia. Chin J Integr Tradit West Med 12:170–172Google Scholar
  66. Sun GX, Williams PN, Carey AM, Zhu YG, Deacon C (2008) Inorganic arsenic in rice bran and its products are an order of magnitude higher than in bulk grain. Environ Sci Technol 42:7542–7546.  https://doi.org/10.1021/es801238p CrossRefPubMedGoogle Scholar
  67. Tetzlaff F, Fischer A (2018) Control of blood vessel formation by Notch signaling. Adv Exp Med Biol 1066:319–338.  https://doi.org/10.1007/978-3-319-89512-3_16 CrossRefPubMedGoogle Scholar
  68. Thurston G, Noguera-Troise I, Yancopoulos GD (2007) The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth. Nat Rev Cancer 7:327–331.  https://doi.org/10.1038/nrc2130 CrossRefPubMedGoogle Scholar
  69. Tomanek RJ, Schatteman GC (2000) Angiogenesis: new insights and therapeutic potential. Anat Rec 261:126–135.  https://doi.org/10.1002/1097-0185(20000615)261:33.0.CO;2-4 CrossRefPubMedGoogle Scholar
  70. Tseng CH (2002) An overview on peripheral vascular disease in blackfoot disease-hyperendemic villages in Taiwan. Angiology 53:529–537.  https://doi.org/10.1177/000331970205300505 CrossRefPubMedGoogle Scholar
  71. Wang X, Jiang F, Mu J, Ye X, Si L (2014) Arsenic trioxide attenuates the invasion potential of human liver cancer cells through the demethylation-activated microRNA-491. Toxicol Lett 227:75–83.  https://doi.org/10.1016/j.toxlet.2014.03.016 CrossRefPubMedGoogle Scholar
  72. Wang W, Li C, Zhang Z, Zhang Y (2019) Arsenic trioxide in synergy with vitamin D rescues the defective VDR-PPAR-gamma functional module of autophagy in rheumatoid arthritis. PPAR Res 2019:6403504.  https://doi.org/10.1155/2019/6403504 CrossRefPubMedPubMedCentralGoogle Scholar
  73. Weis SM, Cheresh DA (2011) Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med 17:1359–1370.  https://doi.org/10.1038/nm.2537 CrossRefPubMedGoogle Scholar
  74. Xiao YF, Liu SX, Wu DD, Chen X, Ren LF (2006) Inhibitory effect of arsenic trioxide on angiogenesis and expression of vascular endothelial growth factor in gastric cancer. World J Gastroenterol 12:5780–5786.  https://doi.org/10.1186/1471-230X-6-26 CrossRefPubMedPubMedCentralGoogle Scholar
  75. Xiao YF, Wu DD, Liu SX, Chen X, Ren LF (2007) Effect of arsenic trioxide on vascular endothelial cell proliferation and expression of vascular endothelial growth factor receptors Flt-1 and KDR in gastric cancer in nude mice. World J Gastroenterol 13:6498–6505.  https://doi.org/10.3748/wjg.13.6498 CrossRefPubMedPubMedCentralGoogle Scholar
  76. Xie SL, Yang MH, Chen K, Huang H, Zhao XW (2015) Efficacy of arsenic trioxide in the treatment of malignant pleural effusion caused by pleural metastasis of lung cancer. Cell Biochem Biophys 71:1325–1333.  https://doi.org/10.1007/s12013-014-0352-3 CrossRefPubMedGoogle Scholar
  77. Yang MH, Zang YS, Huang H, Chen K, Li B (2014) Arsenic trioxide exerts anti-lung cancer activity by inhibiting angiogenesis. Curr Cancer Drug Targets 14:557–566.  https://doi.org/10.2174/1568009614666140725090000 CrossRefPubMedGoogle Scholar
  78. Yang MH, Chang KJ, Zheng JC, Huang H, Sun GY (2017) Anti-angiogenic effect of arsenic trioxide in lung cancer via inhibition of endothelial cell migration, proliferation and tube formation. Oncol Lett 14:3103–3109.  https://doi.org/10.3892/ol.2017.6518 CrossRefPubMedPubMedCentralGoogle Scholar
  79. Zhang J, Li C, Zheng Y, Lin Z, Zhang Y, Zhang Z (2017) Inhibition of angiogenesis by arsenic trioxide via TSP-1-TGF-beta1-CTGF-VEGF functional module in rheumatoid arthritis. Oncotarget 8:73529–73546.  https://doi.org/10.18632/oncotarget.19867 CrossRefPubMedPubMedCentralGoogle Scholar
  80. Zhang J, Zhang Y, Wang W, Li C, Zhang Z (2018a) Double-sided personality: effects of arsenic trioxide on inflammation. Inflammation 41:1128–1134.  https://doi.org/10.1007/s10753-018-0775-x CrossRefPubMedGoogle Scholar
  81. Zhang L, Liu L, Zhan S, Chen L, Wang Y (2018b) Arsenic trioxide suppressed migration and angiogenesis by targeting FOXO3a in gastric cancer cells. Int J Mol Sci.  https://doi.org/10.3390/ijms19123739 CrossRefPubMedPubMedCentralGoogle Scholar
  82. Zhao XY, Yang S, Chen YR, Li PC, Dou MM, Zhang J (2014) Resveratrol and arsenic trioxide act synergistically to kill tumor cells in vitro and in vivo. PLoS ONE 9:e98925.  https://doi.org/10.1371/journal.pone.0098925 CrossRefPubMedPubMedCentralGoogle Scholar
  83. Zhou J, Meng R, Sui X, Meng L, Jia J, Yang B (2005) Effects of administration styles of arsenic trioxide on intracellular arsenic concentration, cell differentiation and apoptosis. Haematologica 90:1277–1279.  https://doi.org/10.1016/j.exphem.2005.06.025 CrossRefPubMedGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2019

Authors and Affiliations

  1. 1.Department of Rheumatology, The First Affiliated HospitalHarbin Medical UniversityHarbinChina

Personalised recommendations