title: JNK1/2 Activation by an Extract from the Roots of Morus alba L. Reduces the Viability of Multidrug-Resistant MCF-7/Dox Cells by Inhibiting YB-1-Dependent MDR1 Expression.
abstract: Cancer cells acquire anticancer drug resistance during chemotherapy, which aggravates cancer disease. MDR1 encoded from multidrug resistance gene 1 mainly causes multidrug resistance phenotypes of different cancer cells. In this study, we demonstrate that JNK1/2 activation by an extract from the root of Morus alba L. (White mulberry) reduces doxorubicin-resistant MCF-7/Dox cell viability by inhibiting YB-1 regulation of MDR1 gene expression. When MCF-7 or MCF-7/Dox cells, where MDR1 is highly expressed were treated with an extract from roots or leaves of Morus alba L., respectively, the root extract from the mulberry (REM) but not the leaf extract (LEM) reduced cell viabilities of both MCF-7 and MCF-7/Dox cells, which was enhanced by cotreatment with doxorubicin. REM but not LEM further inhibited YB-1 nuclear translocation and its regulation of MDR1 gene expression. Moreover, REM promoted phosphorylation of c-Jun NH2-terminal kinase 1/2 (JNK1/2) and JNK1/2 inhibitor, SP600125 and rescued REM inhibition of both MDR1 expression and viabilities in MCF-7/Dox cells. Consistently, overexpression of JNK1, c-Jun, or c-Fos inhibited YB-1-dependent MDR1 expression and reduced viabilities in MCF-7/Dox cells. In conclusion, our data indicate that REM-activated JNK-cJun/c-Fos pathway decreases the viability of MCF-7/Dox cells by inhibiting YB-1-dependent MDR1 gene expression. Thus, we suggest that REM may be useful for treating multidrug-resistant cancer cells.
authors: Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Dongdaemun, Seoul 130-701, Republic of Korea.
authors: Youn Kyung
authors: YK
authors: Choi
authors: Sung-Gook
authors: SG
authors: Cho
authors: Hyeong Sim
authors: HS
authors: Choi
authors: Sang-Mi
authors: SM
authors: Woo
authors: Yee Jin
authors: YJ
authors: Yun
authors: Yong Cheol
authors: YC
authors: Shin
authors: Seong-Gyu
authors: SG
authors: Ko
references: Jpn J Pharmacol. 1976 Aug;26(4):461-9
references: 1003702
references: Cancer Res. 2004 Dec 15;64(24):9057-61
references: 15604272
references: Chem Pharm Bull (Tokyo). 2010 Apr;58(4):568-71
references: 20410645
references: Neoplasia. 2010 Aug;12(8):628-36
references: 20689757
references: Mol Pharmacol. 2004 Apr;65(4):906-16
references: 15044620
references: Biochemistry. 1999 Feb 16;38(7):2189-99
references: 10026303
references: Cancer Chemother Pharmacol. 2010 May;65(6):1131-6
references: 19763573
references: J Biol Chem. 2000 Jan 28;275(4):2979-85
references: 10644769
references: J Natl Cancer Inst. 1989 Sep 20;81(18):1401-5
references: 2778826
references: Cancer Gene Ther. 2009 Jan;16(1):65-72
references: 18654608
references: Chem Pharm Bull (Tokyo). 2010 Feb;58(2):257-60
references: 20118592
references: Mol Cancer. 2009 Jul 31;8:56
references: 19646254
references: Mol Cancer Ther. 2011 Jul;10(7):1289-99
references: 21551263
references: Cancer Res. 1990 Nov 1;50(21):6936-43
references: 2208159
references: Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12384-9
references: 14530393
references: Cancer Res. 2003 Aug 1;63(15):4527-32
references: 12907627
references: Oncogene. 2007 Apr 26;26(19):2736-46
references: 17072343
references: Cancer Res. 1996 Sep 15;56(18):4224-8
references: 8797596
references: Mol Cancer Ther. 2004 Nov;3(11):1485-92
references: 15542787
references: J Pediatr Surg. 2009 Feb;44(2):377-80
references: 19231538
references: J Biochem. 2008 Apr;143(4):517-24
references: 18174186
references: Mol Pharmacol. 1990 Jun;37(6):801-9
references: 1972772
references: Protein Pept Lett. 2012 Aug;19(8):839-45
references: 22762189
references: Arch Pharm Res. 2002 Apr;25(2):191-6
references: 12009034
references: Drug Resist Updat. 2012 Feb-Apr;15(1-2):62-9
references: 22409994
references: Anticancer Res. 1996 Nov-Dec;16(6B):3499-505
references: 9042212
references: Cancer Res. 2006 Jan 1;66(1):445-52
references: 16397260
references: Fitoterapia. 2010 Sep;81(6):614-6
references: 20211228
references: Mol Cell Biol. 2006 Jan;26(1):277-92
references: 16354698
references: Nutr Cancer. 2012 Aug;64(6):889-98
references: 22860924
references: Oncogene. 2005 Jun 16;24(26):4281-92
references: 15806160
references: Chem Biol Interact. 2012 Oct 25;200(1):38-44
references: 22982777
references: Basic Clin Pharmacol Toxicol. 2005 Jan;96(1):80-7
references: 15667600
references: Hepatobiliary Pancreat Dis Int. 2010 Jun;9(3):287-95
references: 20525557
references: Carcinogenesis. 2011 May;32(5):667-75
references: 21296766
references: J Biol Chem. 2007 Jun 15;282(24):17581-6
references: 17452336
references: Clin Cancer Res. 1995 Nov;1(11):1301-10
references: 9815925
references: Nat Med. 1997 Apr;3(4):447-50
references: 9095180
references: Oncologist. 2003;8(5):411-24
references: 14530494
references: J Natl Cancer Inst. 1989 Jan 18;81(2):116-24
references: 2562856