title: Paeonol oxime inhibits bFGF-induced angiogenesis and reduces VEGF levels in fibrosarcoma cells.
abstract: BACKGROUND
  We previously reported the anti-angiogenic activity of paeonol isolated from Moutan Cortex. In the present study, we investigated the negative effect of paeonol oxime (PO, a paeonol derivative) on basic fibroblast growth factor (bFGF)-mediated angiogenesis in human umbilical vein endothelial cells (HUVECs) (including tumor angiogenesis) and pro-survival activity in HT-1080 fibrosarcoma cell line.
  
  
  RESULTS
  We showed that PO (IC(50) = 17.3 microg/ml) significantly inhibited bFGF-induced cell proliferation, which was achieved with higher concentrations of paeonol (IC(50) over 200 microg). The treatment with PO blocked bFGF-stimulated migration and in vitro capillary differentiation (tube formation) in a dose-dependent manner. Furthermore, PO was able to disrupt neovascularization in vivo. Interestingly, PO (25 microg/ml) decreased the cell viability of HT-1080 fibrosarcoma cells but not that of HUVECs. The treatment with PO at 12.5 microg/ml reduced the levels of phosphorylated AKT and VEGF expression (intracellular and extracelluar) in HT-1080 cells. Consistently, immunefluorescence imaging analysis revealed that PO treatment attenuated AKT phosphorylation in HT-1080 cells.
  
  
  CONCLUSIONS
  Taken together, these results suggest that PO inhibits bFGF-induced angiogenesis in HUVECs and decreased the levels of PI3K, phospho-AKT and VEGF in HT-1080 cells.
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Seung-Ae
authors.initials: SA
authors.lastname: Kim
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.forename: Ihn
authors.initials: I
authors.lastname: Han
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jung
authors.forename: Eun-Ok
authors.initials: EO
authors.lastname: Lee
authors.forename: Shudong
authors.initials: S
authors.lastname: Zhu
authors.forename: Chang-Yan
authors.initials: CY
authors.lastname: Chen
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005354:Fibrosarcoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000188:drug therapy*; D010091:Oximes / Q000494:pharmacology* / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D010091:Oximes; D042461:Vascular Endothelial Growth Factor A; C553237:paeonol oxime; D016222:Fibroblast Growth Factor 2; C013638:paeonol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
references.citation: Cell. 1998 Oct 2;95(1):29-39
references.pmid: 9778245
references.citation: Mol Biol Cell. 2005 Sep;16(9):4153-62
references.pmid: 15987743
references.citation: Carcinogenesis. 2006 Dec;27(12):2455-63
references.pmid: 16777983
references.citation: Int J Cancer. 2002 Mar 1;98(1):36-41
references.pmid: 11857382
references.citation: Semin Oncol. 2002 Dec;29(6 Suppl 16):10-4
references.pmid: 12516033
references.citation: Oncogene. 2006 Jan 5;25(1):122-9
references.pmid: 16132039
references.citation: Br J Pharmacol. 2003 Jul;139(6):1146-52
references.pmid: 12871833
references.citation: Ann Surg Oncol. 2001 Apr;8(3):260-7
references.pmid: 11314944
references.citation: J Clin Invest. 1973 Nov;52(11):2745-56
references.pmid: 4355998
references.citation: J Ethnopharmacol. 2006 Jun 30;106(2):208-15
references.pmid: 16458462
references.citation: FASEB J. 2006 Oct;20(12):2009-16
references.pmid: 17012253
references.citation: Biol Pharm Bull. 2005 Jan;28(1):27-31
references.pmid: 15635158
references.citation: Biol Pharm Bull. 2009 Jul;32(7):1142-7
references.pmid: 19571375
references.citation: Anticancer Drugs. 2008 Apr;19(4):401-9
references.pmid: 18454050
references.citation: Int Immunopharmacol. 2004 Feb;4(2):279-87
references.pmid: 14996419
references.citation: Blood. 2007 Jan 15;109(2):560-5
references.pmid: 16990598
references.citation: Science. 2002 Mar 29;295(5564):2387-92
references.pmid: 11923519
references.citation: J Immunol Methods. 1983 Dec 16;65(1-2):55-63
references.pmid: 6606682
references.citation: J Mol Signal. 2008 Mar 20;3:7
references.pmid: 18355401
references.citation: Zhong Yao Cai. 1997 Dec;20(12):626-8
references.pmid: 12572506
references.citation: Chem Biol Interact. 2005 Oct 20;156(2-3):141-50
references.pmid: 16169542
references.citation: Ann Oncol. 1994;5 Suppl 4:45-50
references.pmid: 7520262
references.citation: Int J Cancer. 2007 Jun 1;120(11):2481-90
references.pmid: 17311288
references.citation: Inflamm Res. 2008 Apr;57(4):189-98
references.pmid: 18363035
references.citation: J Pathol. 2005 Mar;205(4):530-6
references.pmid: 15714461
references.citation: J Clin Oncol. 2000 Mar;18(5):1135-49
references.pmid: 10694567
references.citation: Recent Results Cancer Res. 2010;180:51-81
references.pmid: 20033378
references.citation: Int J Cancer. 1996 Jul 3;67(1):148-52
references.pmid: 8690516
references.citation: Br J Cancer. 2001 Jun 15;84(12):1610-5
references.pmid: 11401313
references.citation: Carcinogenesis. 2005 Aug;26(8):1436-45
references.pmid: 15845650
references.citation: Cell. 1989 Sep 8;58(5):933-43
references.pmid: 2528412
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1749-53
references.pmid: 10677529