KLF4 promotes hydrogen-peroxide-induced apoptosis of chronic myeloid leukemia cells involving the bcl-2/bax pathway.
K562 cells and peripheral blood mononuclear cells were treated with hydrogen peroxide (H(2)O(2)) to determine the expression of Krüppel-like factor (KLF) 4. A full-length complementary DNA or an anti-sense oligonucleotide of KLF4 was transfected into cells, and expressions of B-cell lymphoma/leukemia-2 (bcl-2) and bcl-2-associated X (bax) proteins were analyzed. The results showed that H(2)O(2) treatment of cells resulted in an increase in KLF4 levels; KLF4 induced apoptosis and slowed cell growth, potentially resulting from up-regulation of bax and down-regulation of bcl-2. Transcriptional activities on bcl-2 and bax were promoted following KLF4 overexpression potentially through KLF4 binding sites on corresponding promoters. All results indicate that KLF4 induces apoptosis in leukemia cells involving the bcl-2/bax pathway during H(2)O(2) stimulation, suggesting a potential mechanism for research on drug-induced apoptosis.
Li
Zhongdong
Z
Department of Hematology, Renmin Hospital of Jiaozuo, Jiaozuo, Henan, 454150, People's Republic of China.
Zhao
Jie
J
Li
Quanmin
Q
Yang
Wenqi
W
Song
Qinglin
Q
Li
Wenyong
W
Liu
Junwen
J
D017209:Apoptosis; D001665:Binding Sites; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D020014:K562 Cells; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; D053148:Caspase 3
Nat Cell Biol. 2005 Nov;7(11):1074-82
16244670
Oncogene. 2003 Nov 24;22(53):8590-607
14634621
Cell Prolif. 1991 Mar;24(2):203-14
2009322
Biochem Biophys Res Commun. 2003 Aug 22;308(2):251-6
12901861
Mol Cell Biol. 1995 Nov;15(11):5957-65
7565748
FEBS Lett. 2000 May 4;473(1):95-100
10802067
Blood. 1975 Mar;45(3):321-34
163658
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2007 Dec;32(6):1002-6
18182717
J Pharmacol Exp Ther. 2001 Jan;296(1):1-6
11123355
Science. 2004 Feb 13;303(5660):1010-4
14963330
J Immunol Methods. 1993 Feb 26;159(1-2):93-100
8445268
J Biol Chem. 2006 Aug 11;281(32):23003-12
16717086
J Biol Chem. 2001 Aug 3;276(31):29299-306
11375995
Shock. 2008 Sep;30(3):260-6
18197146
J Biol Chem. 1998 Dec 11;273(50):33750-8
9837963
Nucleic Acids Res. 2000 Aug 1;28(15):2969-76
10908361
Curr Biol. 2000 Oct 5;10(19):1201-4
11050388
Oncogene. 2000 Nov 2;19(46):5259-69
11077443
Cancer Res. 2004 Jun 1;64(11):3838-43
15172991
Nucleic Acids Res. 2007;35(18):6137-49
17827213
Leuk Lymphoma. 1999 May;33(5-6):499-509
10342577
Biochem Biophys Res Commun. 2007 Oct 26;362(3):575-81
17719562
Cell Res. 2005 Feb;15(2):92-6
15740636
Nat Genet. 2003 May;34(1):85-90
12704389
Blood. 1997 Dec 15;90(12):4901-9
9389707
Blood. 1999 Apr 15;93(8):2671-8
10194447
J Biol Chem. 2003 Nov 28;278(48):48004-11
12970361