Propranolol induces regression of hemangioma cells via the down-regulation of the PI3K/Akt/eNOS/VEGF pathway

Pediatric Blood and Cancer

Volumn 62, Issue 8, 2015, Pages 1414-1420

  Pan, Wei Kang ^a   Li, Peng ^a   Guo, Zheng Tuan ^a   Huang, Qiang ^a   Gao, Ya ^a  

^a THE SECOND AFFILIATED HOSPITAL OF XI AN JIAOTONG UNIVERSITY   (China)

Author keywords

ENOS; Infantile hemangioma; Propranolol; VEGF

Indexed keywords

COFILIN; CYCLIN A2; CYCLIN D2; ENDOTHELIAL NITRIC OXIDE SYNTHASE; GELATINASE B; MATRIGEL; NITRIC OXIDE; NORADRENALIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROPRANOLOL; PROTEIN KINASE B; PROTEIN P21; PROTEIN P27; VASCULOTROPIN; VASCULOTROPIN RECEPTOR 2; 2-(4-MORPHOLINYL)-8-PHENYL-4H-1-BENZOPYRAN-4-ONE; ANGIOGENESIS INHIBITOR; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CCNA2 PROTEIN, HUMAN; CCND2 PROTEIN, HUMAN; CHROMONE DERIVATIVE; CINNAMIC ACID DERIVATIVE; CYCLIN DEPENDENT KINASE INHIBITOR 1A; CYCLINE; FLT1 PROTEIN, HUMAN; MORPHOLINE DERIVATIVE; N(G) NITROARGININE METHYL ESTER; NOS3 PROTEIN, HUMAN; P27 ANTIGEN; SU 1498; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2, HUMAN; VASCULOTROPIN A; VASCULOTROPIN RECEPTOR 1; VEGFA PROTEIN, HUMAN;

ANTIANGIOGENIC ACTIVITY; ARTICLE; CAPILLARY HEMANGIOMA; CELL CYCLE PROGRESSION; CELL INVASION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; DOWN REGULATION; ENDOTHELIUM CELL; FLOW CYTOMETER; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; WESTERN BLOTTING; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; CELL CULTURE; CELL CYCLE CHECKPOINT; CELL PROLIFERATION; DRUG EFFECTS; HEMANGIOMA; INFANT; METABOLISM; NEOVASCULARIZATION, PATHOLOGIC; NEWBORN; PATHOLOGY; PERICYTE; PHOSPHORYLATION; TUMOR INVASION;

ADRENERGIC BETA-ANTAGONISTS; ANGIOGENESIS INHIBITORS; CELL CYCLE CHECKPOINTS; CELL PROLIFERATION; CELLS, CULTURED; CHROMONES; CINNAMATES; CYCLIN A2; CYCLIN D2; CYCLIN-DEPENDENT KINASE INHIBITOR P21; ENDOTHELIAL CELLS; HEMANGIOMA; HUMANS; INFANT; INFANT, NEWBORN; MORPHOLINES; NEOPLASM INVASIVENESS; NEOVASCULARIZATION, PATHOLOGIC; NG-NITROARGININE METHYL ESTER; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE III; NOREPINEPHRINE; PERICYTES; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHORYLATION; PROLIFERATING CELL NUCLEAR ANTIGEN; PROPRANOLOL; PROTO-ONCOGENE PROTEINS C-AKT; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 84932175342     PISSN: 15455009     EISSN: 15455017     Source Type: Journal    
DOI: 10.1002/pbc.25453     Document Type: Article

References (48)

1. Bruckner AL, Frieden IJ. Hemangiomas of infancy. J Am Acad Dermatol 2003; 48:477-493.
2. Drolet BA, Esterly NB, Frieden IJ. Hemangiomas in children. N Eng J Med 1999; 341:173-181.
3. Zou HX, Jia J, Zhang WF, Sun ZJ, Zhao YF. Propranolol inhibits endothelial progenitor cell homing: A possible treatment mechanism of infantile hemangioma. Cardiovasc Pathol 2013; 22:203-210.
4. Frieden IJ, Eichenfield LF, Esterly NB, Geronemus R, Mallory SB. Guidelines of care for hemangiomas of infancy. American Academy of Dermatology Guidelines/Outcomes Committee. J Am Acad Dermatol 1997; 37:631-637.
5. Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, Horii KA, Lucky AW, Mancini AJ, Metry DW, Newell B, Nopper AJ, Frieden IJ. Prospective study of infantile hemangiomas: Clinical characteristics predicting complications and treatment. Pediatrics 2006; 118:882-887.
6. Margileth AM, Museles M. Cutaneous hemangiomas in children. Diagnosis and conservative management. JAMA 1965; 194:523-526.
7. Greenberger S, Bischoff J. Pathogenesis of infantile haemangioma. Br J Dermatol 2013; 169:12-19.
8. Boscolo E, Bischoff J. Vasculogenesis in infantile hemangioma. Angiogenesis 2009; 12:197-207.
9. Millauer B, Shawver LK, Plate KH, Risau W, Ullrich A. Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature 1994; 367:576-579.
10. Lamy S, Lachambre MP, Lord-Dufour S, Beliveau R. Propranolol suppresses angiogenesis in vitro: Inhibition of proliferation, migration, and differentiation of endothelial cells. Vasc Pharmacol 2010; 53:200-208.
11. Plate KH, Breier G, Weich HA, Risau W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 1992; 359:845-848.
12. Liekens S, De Clercq E, Neyts J. Angiogenesis: Regulators and clinical applications. Biochem Pharmacol 2001; 61:253-270.
13. de Graaf M, Totte JE, van Os-Medendorp H, van Renselaar W, Breugem CC, Pasmans SG. Treatment of infantile hemangioma in regional hospitals with ehealth support: Evaluation of feasibility and acceptance by parents and doctors. JMIR Res Protoc 2014; 3:e52.
14. Malozowski S, Nelson L, Calis KA. More on ovarian insufficiency with imatinib. N Eng J Med 2008; 358:2648-2649.
15. Yuan WL, Jin ZL, Wei JJ, Liu ZY, Xue L, Wang XK. Propranolol given orally for proliferating infantile haemangiomas: Analysis of efficacy and serological changes in vascular endothelial growth factor and endothelial nitric oxide synthase in 35 patients. Br J Oral Maxillo Fac Surg 2013; 51:656-661.
16. McSwiney E, Murray D, Murphy M. Propranolol therapy for cutaneous infantile haemangiomas initiated safely as a day-case procedure. Eur J Pediatr 2014; 173:63-68.
17. Zhang L, Mai HM, Zheng J, Zheng JW, Wang YA, Qin ZP, Li KL. Propranolol inhibits angiogenesis via down-regulating the expression of vascular endothelial growth factor in hemangioma derived stem cell. Int J Clin Exp Pathol 2014; 7:48-55.
18. Kang Z, Jiang W, Luan H, Zhao F, Zhang S. Cornin induces angiogenesis through PI3K-Akt-eNOS-VEGF signaling pathway. Food Chem Toxicol 2013; 58:340-346.
19. Munoz-Chapuli R, Quesada AR, Angel Medina M. Angiogenesis and signal transduction in endothelial cells. Cell Mol Life Sci: CMLS 2004; 61:2224-2243.
20. Radisavljevic Z, Avraham H, Avraham S. Vascular endothelial growth factor up-regulates ICAM-1 expression via the phosphatidylinositol 3 OH-kinase/AKT/Nitric oxide pathway and modulates migration of brain microvascular endothelial cells. J Biol Chem 2000; 275:20770-20774.
21. Simao F, Pagnussat AS, Seo JH, Navaratna D, Leung W, Lok J, Guo S, Waeber C, Salbego CG, Lo EH. Pro-angiogenic effects of resveratrol in brain endothelial cells: nitric oxide-mediated regulation of vascular endothelial growth factor and metalloproteinases. J Cereb Blood Flow Metab 2012; 32:884-895.
22. Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992; 359:843-845.
23. Chen J, Cui X, Zacharek A, Jiang H, Roberts C, Zhang C, Lu M, Kapke A, Feldkamp CS, Chopp M. Niaspan increases angiogenesis and improves functional recovery after stroke. Ann Neurol 2007; 62:49-58.
24. Pasquier E, Street J, Pouchy C, Carre M, Gifford AJ, Murray J, Norris MD, Trahair T, Andre N, Kavallaris M. Beta-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma. Br J Cancer 2013; 108:2485-2494.
25. Sood AK, Bhatty R, Kamat AA, Landen CN, Han L, Thaker PH, Li Y, Gershenson DM, Lutgendorf S, Cole SW. Stress hormone-mediated invasion of ovarian cancer cells. Clin Cancer Res 2006; 12:369-375.
26. Entschladen F, Drell TLt, Lang K, Joseph J, Zaenker KS. Tumour-cell migration, invasion, and metastasis: Navigation by neurotransmitters. Lancet Oncol 2004; 5:254-258.
27. Li P, Xiao X, Xu Q, Guo Z. Establishment of human infancy hemangioma-derived endothelial cell line XPTS-1 and animal model of human infancy hemangioma. Chin J Stomatol 2011; 46:129-133.
28. Greenberger S, Adini I, Boscolo E, Mulliken JB, Bischoff J. Targeting NF-kappaB in infantile hemangioma-derived stem cells reduces VEGF-A expression. Angiogenesis 2010; 13:327-335.
29. Ji Y, Chen S, Li K, Xiao X, Zheng S, Xu T. The role of beta-adrenergic receptor signaling in the proliferation of hemangioma-derived endothelial cells. Cell Div 2013; 8:1.
30. Guo K, Ma Q, Wang L, Hu H, Li J, Zhang D, Zhang M. Norepinephrine-induced invasion by pancreatic cancer cells is inhibited by propranolol. Oncol Rep 2009; 22:825-830.
31. Stiles J, Amaya C, Pham R, Rowntree RK, Lacaze M, Mulne A, Bischoff J, Kokta V, Boucheron LE, Mitchell DC, Bryan BA. Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis. Exp Ther Med 2012; 4:594-604.
32. Huang XY, Wang HC, Yuan Z, Huang J, Zheng Q. Norepinephrine stimulates pancreatic cancer cell proliferation, migration and invasion via beta-adrenergic receptor-dependent activation of P38/MAPK pathway. Hepatogastroenterology 2012; 59:889-893.
33. Marler JJ, Fishman SJ, Kilroy SM, Fang J, Upton J, Mulliken JB, Burrows PE, Zurakowski D, Folkman J, Moses MA. Increased expression of urinary matrix metalloproteinases parallels the extent and activity of vascular anomalies. Pediatrics 2005; 116:38-45.
34. Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: Insights into the molecular mechanisms of action. Br J Dermatol 2010; 163:269-274.
35. Zhang L, Lin X, Wang W, Zhuang X, Dong J, Qi Z. Circulating level of vascular endothelial growth factor in differentiating hemangioma from vascular malformation patients. Plast Reconstr Surg 2005; 116:200-204.
36. Yang EV, Sood AK, Chen M, Li Y, Eubank TD, Marsh CB, Jewell S, Flavahan NA, Morrison C, Yeh PE, Lemeshow S, Glaser R. Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells. Cancer Res 2006; 66:10357-10364.
37. Thaivalappil S, Bauman N, Saieg A, Movius E, Brown KJ, Preciado D. Propranolol-mediated attenuation of MMP-9 excretion in infants with hemangiomas. JAMA Otolaryngol Head Neck Surg 2013; 139:1026-1031.
38. Al-Wadei HA, Al-Wadei MH, Schuller HM. Prevention of pancreatic cancer by the beta-blocker propranolol. Anti-Cancer Drugs 2009; 20:477-482.
39. Park SY, Kang JH, Jeong KJ, Lee J, Han JW, Choi WS, Kim YK, Kang J, Park CG, Lee HY. Norepinephrine induces VEGF expression and angiogenesis by a hypoxia-inducible factor-1alpha protein-dependent mechanism. Int J Cancer 2011; 128:2306-2316.
40. Bamburg JR, Wiggan OP. ADF/cofilin and actin dynamics in disease. Trends Cell Biol 2002; 12:598-605.
41. Arber S, Barbayannis FA, Hanser H, Schneider C, Stanyon CA, Bernard O, Caroni P. Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature 1998; 393:805-809.
42. Street CA, Bryan BA. Rho kinase proteins-pleiotropic modulators of cell survival and apoptosis. Anticancer Res 2011; 31:3645-3657.
43. Jiang Q, Ding S, Wu J, Liu X, Wu Z. Norepinephrine stimulates mobilization of endothelial progenitor cells after limb ischemia. PloS ONE 2014; 9:e101774.
44. Dai Y, Hou F, Buckmiller L, Fan CY, Saad A, Suen J, Richter GT. Decreased eNOS protein expression in involuting and propranolol-treated hemangiomas. Arch Otolaryngol Head Neck Surg 2012; 138:177-182.
45. Albinana V, Recio-Poveda L, Zarrabeitia R, Bernabeu C, Botella LM. Propranolol as antiangiogenic candidate for the therapy of hereditary haemorrhagic telangiectasia. Thromb Haemost 2012; 108:41-53.
46. Xiao M, Men LN, Xu MG, Wang GB, Lv HT, Liu C. Berberine protects endothelial progenitor cell from damage of TNF-alpha via the PI3K/AKT/eNOS signaling pathway. Eur J Pharmacol 2014; 743:11-16.
47. Francis SC, Raizada MK, Mangi AA, Melo LG, Dzau VJ, Vale PR, Isner JM, Losordo DW, Chao J, Katovich MJ, Berecek KH. Genetic targeting for cardiovascular therapeutics: Are we near the summit or just beginning the climb. Physiol Genomics 2001; 7:79-94.
48. Barbieri A, Palma G, Rosati A, Giudice A, Falco A, Petrillo A, Petrillo M, Bimonte S, Di Benedetto M, Esposito G, Stiuso P, Abbruzzese A, Caraglia M, Arra C. Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth. J Cell Mol Med 2012; 16:920-926.