title: Natura-alpha targets forkhead box m1 and inhibits androgen-dependent and -independent prostate cancer growth and invasion.
abstract: OBJECTIVE
  The development of new effective therapeutic agents with minimal side effects for prostate cancer (PC) treatment is much needed. Indirubin, an active molecule identified in the traditional Chinese herbal medicine-Qing Dai (Indigo naturalis), has been used to treat leukemia for decades. However, the anticancer properties of Natura-alpha, an indirubin derivative, are not well studied in solid tumors, particularly in PC.
  
  
  METHODS
  The growth kinetics and invasion ability of on human PC cell lines with or without Natura-alpha treatment were measured by cell proliferation and invasion assays. The antitumor effects of Natura-alpha were examined in nude mice tumor xenograft models, and in a patient with advanced hormone-refractory metastatic PC. Signal network proteins targeted by Natura-alpha were analyzed by using proteomic pathway array analysis (PPAA) on xenografts.
  
  
  RESULTS
  Natura-alpha inhibited the growth of both androgen-dependent (LNCaP) and androgen-independent (LNCaP-AI, PC-3, and DU145) PC cells with IC(50) between 4 to 10 mmol/L, and also inhibited invasion of androgen-independent PC cells. Its antitumor effects were further evident in in vivo tumor reduction in androgen-dependent and androgen-independent nude mice tumor xenograft models and reduced tumor volume in the patient with hormone refractory metastatic PC. PPAA revealed that antiproliferative and antiinvasive activities of Natura-alpha on PC might primarily be through its downregulation of Forkhead box M1 (FOXM1) protein. Forced overexpression of FOXM1 largely reversed the inhibition of growth and invasion by Natura-alpha.
  
  
  CONCLUSIONS
  Natura-alpha could serve as a novel and effective therapeutic agent for treatment of both hormone-sensitive and hormone-refractory PC with minimal side effects.
authors: Department of Pathology, New York University School of Medicine, New York, New York, USA.
authors: Yirong
authors: Y
authors: Li
authors: Martin
authors: M
authors: Ligr
authors: James P
authors: JP
authors: McCarron
authors: Garrett
authors: G
authors: Daniels
authors: David
authors: D
authors: Zhang
authors: Xin
authors: X
authors: Zhao
authors: Fei
authors: F
authors: Ye
authors: Jinhua
authors: J
authors: Wang
authors: Xiaomei
authors: X
authors: Liu
authors: Iman
authors: I
authors: Osman
authors: Simon K
authors: SK
authors: Mencher
authors: Hebert
authors: H
authors: Lepor
authors: Long G
authors: LG
authors: Wang
authors: Anna
authors: A
authors: Ferrari
authors: Peng
authors: P
authors: Lee
references: Biomed Environ Sci. 1991 Sep;4(3):332-7
references: 1764225
references: Eur J Immunol. 2010 Feb;40(2):460-9
references: 20077403
references: Science. 1994 Dec 16;266(5192):1821-8
references: 7997877
references: Carcinogenesis. 2006 Oct;27(10):2124-32
references: 16704988
references: Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5236-41
references: 18356297
references: Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8804-8
references: 11438715
references: Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):3937-42
references: 15217923
references: Int J Radiat Oncol Biol Phys. 2010 Aug 1;77(5):1518-26
references: 19906497
references: Int J Cancer. 2000 Feb 1;85(3):446-50
references: 10652439
references: Nat Rev Cancer. 2007 Nov;7(11):847-59
references: 17943136
references: Curr Cancer Drug Targets. 2008 Feb;8(1):53-75
references: 18288944
references: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references: 10655437
references: Biol Chem. 2007 Dec;388(12):1257-74
references: 18020943
references: Cancer Chemother Biol Response Modif. 2002;20:169-96
references: 12703205
references: J Natl Cancer Inst. 1994 Oct 19;86(20):1517-24
references: 7932806
references: Nat Rev Cancer. 2008 Apr;8(4):253-67
references: 18354415
references: Curr Med Chem. 1999 Sep;6(9):859-75
references: 10495356
references: Clin Cancer Res. 2007 Apr 1;13(7):1955-60
references: 17404075
references: Eur J Cancer. 2008 Jan;44(1):46-53
references: 17945478
references: Expert Opin Ther Targets. 2008 Jun;12(6):663-5
references: 18479213
references: Stem Cells. 1994 Jan;12(1):53-63
references: 8142920
references: Nat Clin Pract Gastroenterol Hepatol. 2006 Jul;3(7):390-407
references: 16819502
references: Biochim Biophys Acta. 2007 Aug;1773(8):1263-84
references: 17126425
references: J Biol Chem. 1999 Apr 2;274(14):9656-64
references: 10092652
references: Nat Cell Biol. 2005 Feb;7(2):126-36
references: 15654331
references: Mol Cell Biol. 2004 Apr;24(7):2649-61
references: 15024056
references: CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49
references: 19474385
references: Mol Cancer Ther. 2009 Mar;8(3):582-91
references: 19276163
references: Br J Cancer. 2003 Oct 20;89(8):1566-73
references: 14562033
references: Curr Opin Biotechnol. 1995 Dec;6(6):657-61
references: 8527836
references: J Exp Clin Cancer Res. 2007 Dec;26(4):443-9
references: 18365537
references: Cancer Res. 2006 Oct 1;66(19):9731-5
references: 17018632
references: Cell Div. 2006 May 12;1:6
references: 16759361
references: Am J Pathol. 1999 Sep;155(3):787-98
references: 10487836
references: Am J Surg Pathol. 2003 Nov;27(11):1418-28
references: 14576474
references: Cancer Res. 2009 Apr 15;69(8):3332-8
references: 19351848
references: Harefuah. 2006 Oct;145(10):763-7, 781, 780
references: 17111715
references: Surg Oncol. 2006 Nov;15(3):117-28
references: 17150354
references: Nat Med. 1995 Dec;1(12):1245-6
references: 7489399
references: Cancer Res. 2001 Oct 15;61(20):7544-51
references: 11606392
references: J Cell Physiol. 1999 Jun;179(3):336-46
references: 10228952
references: Genetics. 2008 May;179(1):59-68
references: 18493040
references: Eur J Pharmacol. 2010 Feb 10;627(1-3):348-53
references: 19903468
references: Oncogene. 2008 May 15;27(22):3201-10
references: 18193092