Biochanin A reduces drug-induced p75NTR expression and enhances cell survival: a new in vitro assay for screening inhibitors of p75NTR expression.
Following spinal cord injury (SCI) or peripheral neuropathy, increased levels of the p75(NTR) death receptor initiate the signal transduction cascade leading to cell death. Investigations of compounds that may ameliorate neuronal cell death have largely used rodent models, which are time consuming, expensive, and cumbersome to perform. Previous studies had demonstrated that steroids, particularly dexamethasone and its analog methylprednisolone sodium succinate, exhibit limited neuroprotective effects against neuronal injury. Significantly, many naturally occurring nonsteroidal plant compounds exhibit structural overlap with steroids. In this report, we present an in vitro cellular screen model to practically examine the efficacy of various phytoestrogens in modulating the ibuprofen-induced expression of p75(NTR) and reduced cell survival of CCFSTTG1 and U87MG cells in a rescue (postinjury) or prevention (preinjury) regimen. We show that the phytoestrogen, biochanin A, and, to a lesser extent, genistein are more effective than dexamethasone at reducing p75(NTR) expression and improving the viability of U87MG and CCFSTTG1 before and after p75(NTR) induction. Furthermore, these studies implicate biochanin A's inactivation of p38-MAPK as a possible contributor to reducing p75(NTR) with associated increased cell survival. This new in vitro assay facilitates a more time-efficient screening of compounds to suppress p75(NTR) expression and increase neuronal cell viability prior to their evaluation in animal models of neurological diseases.
El Touny
Lara H
LH
Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
Henderson
Fraser
F
Djakiew
Daniel
D
D001681:Biological Assay / Q000379:methods*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004789:Enzyme Activation / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D034741:RNA, Small Interfering; D017475:Receptors, Nerve Growth Factor; D003907:Dexamethasone; D019833:Genistein; D048051:p38 Mitogen-Activated Protein Kinases; C004541:biochanin A; D007052:Ibuprofen
Science. 1994 Sep 9;265(5178):1596-9
8079174
Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16379-84
16260722
Mol Carcinog. 2001 May;31(1):46-55
11398197
Exp Neurol. 2003 Oct;183(2):286-97
14552870
Brain Res Brain Res Rev. 2001 Nov;37(1-3):372-82
11744101
Cancer Res. 2007 Dec 1;67(23):11402-10
18056468
Cancer Res. 2004 Sep 1;64(17):6207-13
15342406
Physiol Rev. 1999 Jan;79(1):143-80
9922370
Cancer Res. 2007 Apr 1;67(7):3254-62
17409433
Nutr Rev. 2003 Jan;61(1):1-33
12638461
Brain Res. 2007 Mar 16;1137(1):146-52
17204255
Cleve Clin J Med. 2004 Feb;71 Suppl 2:S4-10
15379294
Ann Thorac Surg. 2003 Jul;76(1):315-21
12842576
Nat Neurosci. 2002 Nov;5(11):1131-6
12404007
Spine (Phila Pa 1976). 2001 Feb 15;26(4):426-30
11224891
J Neurosci. 2007 Jul 18;27(29):7751-61
17634369
Biochem Biophys Res Commun. 2006 Mar 24;341(4):1184-92
16460673
Am J Phys Med Rehabil. 2006 Aug;85(8):678-84; quiz 685-7
16865023
J Comp Neurol. 1993 Dec 22;338(4):560-74
8132861
J Neurosci. 2001 May 15;21(10):3492-502
11331378
Clin Cancer Res. 2000 Jan;6(1):230-6
10656454
Brain Res Mol Brain Res. 2001 Feb 19;87(1):61-70
11223160
Pharmacol Ther. 2007 Oct;116(1):77-106
17659348
J Neurotrauma. 2000 Oct;17(10):915-25
11063057
Mol Pain. 2007 Nov 01;3:33
17974036
Pharm Res. 2008 Sep;25(9):2158-63
18454305
Trends Neurosci. 2005 Jan;28(1):5-11
15626491
Exp Neurol. 2008 Oct;213(2):257-67
18590729
J Neurotrauma. 2006 Jun;23(6):830-52
16774470
Food Addit Contam. 1985 Apr-Jun;2(2):73-106
4018320
Endocrinology. 1997 Mar;138(3):863-70
9048584
Spine (Phila Pa 1976). 2006 Dec 15;31(26):2992-6; discussion 2997
17172994
J Neurochem. 2003 Mar;84(6):1340-8
12614334
J Nutr. 2003 Jul;133(7):2367-76
12840208
Spine J. 2004 Jul-Aug;4(4):451-64
15246307
Exp Neurol. 1996 Jan;137(1):119-26
8566203
Int J Cancer. 2003 May 20;105(1):47-52
12672029
J Neurosurg. 1991 Jul;75(1):15-26
2045903
Pharmacol Rev. 2001 Mar;53(1):135-59
11171943
AAPS J. 2006 Jul 07;8(3):E433-42
17025260
Eur J Neurosci. 1994 May 1;6(5):712-24
8075816
J Neurosci Res. 2001 Apr 1;64(1):11-7
11276046
Science. 1996 Apr 26;272(5261):542-5
8614802
Exp Cell Res. 2005 Mar 10;304(1):69-80
15707575
J Altern Complement Med. 2008 Apr;14(3):287-97
18370585
JAMA. 1997 May 28;277(20):1597-604
9168289
J Neurosci. 2006 Apr 19;26(16):4308-17
16624951
Acta Anaesthesiol Belg. 1987;38(4):405-9
3327343