scholarly journals Down-Regulation of Osteoclast Differentiation by Daidzein via Caspase 3

2002 ◽  
Vol 17 (4) ◽  
pp. 630-638 ◽  
Author(s):  
Claudia Maria Rassi ◽  
Michele Lieberherr ◽  
Gilles Chaumaz ◽  
Alain Pointillart ◽  
Giulia Cournot
Keyword(s):  
Caspase 3 ◽  
Osteoclast Differentiation ◽  
Down Regulation

Active caspase-3 is required for osteoclast differentiation

2006 ◽  
Vol 209 (3) ◽  
pp. 836-844 ◽  
Author(s):  
K.H. Szymczyk ◽  
T.A. Freeman ◽  
C.S. Adams ◽  
V. Srinivas ◽  
M.J. Steinbeck
Keyword(s):  
Caspase 3 ◽  
Osteoclast Differentiation ◽  
Active Caspase

Immunosuppressant PG490 (triptolide) induces apoptosis through the activation of caspase-3 and down-regulation of XIAP in U937 cells

2003 ◽  
Vol 66 (2) ◽  
pp. 273-280 ◽  
Author(s):  
Yun-Jung Choi ◽  
Tae Gyu Kim ◽  
Young-Ho Kim ◽  
Sung-Hee Lee ◽  
Young Kyu Kwon ◽  
...  
Keyword(s):  
Caspase 3 ◽  
U937 Cells ◽  
Down Regulation

scholarly journals Down-Regulation of Telomerase Activity and Activation of Caspase-3 Are Responsible for Tanshinone I-Induced Apoptosis in Monocyte Leukemia Cells in Vitro

2010 ◽  
Vol 11 (6) ◽  
pp. 2267-2280 ◽  
Author(s):  
Xiao-Dan Liu ◽  
Rui-Fang Fan ◽  
Yong Zhang ◽  
Hong-Zhi Yang ◽  
Zhi-Gang Fang ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Telomerase Activity ◽  
Leukemia Cells ◽  
Down Regulation ◽  
Tanshinone I ◽  
Induced Apoptosis

9-Hydroxy-6,7-dimethoxydalbergiquinol inhibits osteoclast differentiation through down-regulation of Akt, c-Fos and NFATc1

2014 ◽  
Vol 20 (1) ◽  
pp. 213-220 ◽  
Author(s):  
Ju-Young Kim ◽  
Jung Young Kim ◽  
Yoon-Hee Cheon ◽  
Sung Chul Kwak ◽  
Jong Min Baek ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Down Regulation

Inactivation of JAK/STAT Cell Signaling by SK-7041, a Novel HDAC Inhibitor, Effectively Inhibits Growth of Acute Myeloid Leukemia Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4005-4005
Author(s):  
Byung-Su Kim ◽  
Chansu Lee ◽  
Juwon Park ◽  
Kwang-Sung Ahn ◽  
Byoung Kook Kim ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Hdac Inhibitor ◽  
Caspase 3 ◽  
Combined Treatment ◽  
Down Regulation ◽  
Anti Cancer ◽  
Acute Myeloid Leukemia Cells ◽  
Kg1 Cells ◽  
Immunoblotting Technique ◽  
Stat Pathway

Abstract Activation of the JAK/STAT pathway appears common in AML, occurring in up to 70% of AML patients. Therefore, JAK/STAT signal inhibitors are promising as candidate anti-cancer agents in AML. Recently, we reported that SK-7041, an HDAC inhibitor, inhibited the growth of AML cells via activation of caspase-3 and down-regulation of cyclin D1. These findings lead us to further examine whether SK-7041 inhibits the growth of KG1 AML cells via inactivation of JAK/STAT signals. Multi-immunoblotting technique (Kinetworks™ analysis) showed that expression of p-STAT-3, p-STAT-5, and p-Erk was down-regulated in KG1 cells treated with SK-7041. These results were confirmed by individual western blot analysis. In addition, IL-6-induced activation of STAT-3 and Erk was inhibited by treatment of SK-7041. Combined treatment of SK-7041 and JAK inhibitor (AG490) showed additive anti-leukemic effect as evidenced by caspase-3 activation, down-regulation of cyclin D1 (cMYC), and inhibition of phosphorylation of STATs (−1, −3). These results suggest that HDAC inhibitor, SK-7041, inhibited AML cell growth via inactivation of JAK/STATs pathway.

Obatoclax (GX15-070) Overcomes Glucocorticoid-Resistance In Acute Lymphoblastic Leukemia through Induction of Apoptosis and Autophagy

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1809-1809
Author(s):  
Hisashi Harada ◽  
Nastaran Heidari ◽  
Mark Hicks
Keyword(s):  
Cell Death ◽  
Acute Lymphoblastic Leukemia ◽  
Small Molecule ◽  
Caspase 3 ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Annexin V ◽  
Glucocorticoid Resistance ◽  
Down Regulation

Abstract Abstract 1809 Glucocorticoids (GC) are common components in many chemotherapeutic protocols for lymphoid/myeloid malignancies, including acute lymphoblastic leukemia (ALL). However, patients often develop resistance to GC on relapse. Resistance to GC in ALL can be associated with defects in apoptosis machinery, but not in the GC receptor. Thus, targeting downstream molecules may lead to the development of new therapeutic strategies. GC-induced apoptosis is through the intrinsic mitochondria-dependent pathway. The BCL-2 family proteins are central regulatory proteins in this pathway. We hypothesized that targeting anti-apoptotic MCL-1 might be effective among the BCL-2 family proteins, since (1) we recognized that treatment with dexamethasone (Dex) in CCRF-CEM or Molt-4 T-ALL cells slightly induce MCL-1 and the expression level of MCL-1 is higher in Dex-resistant ALL cells compared with that in Dex-sensitive cells; (2) recent studies have demonstrated that increased expression of MCL-1 associates with GC resistance. In support of our hypothesis, down-regulation of MCL-1 by shRNA enhances Dex-induced cell death. We then pharmacologically inactivate MCL-1 function by GX15-070 (obatoclax), a BH3 mimetic small molecule that targets anti-apoptotic BCL-2 family proteins including BCL-2, BCL-XL, and MCL-1. Treatment with GX15-070 in both Dex-sensitive and -resistant ALL cells shows effective growth inhibition and cell death. GX15-070 induces caspase-3 cleavage and increases Annexin V-positive population, indicative of apoptosis. Before the onset of apoptosis, GX15-070 induces LC3 conversion as well as p62 degradation, both of which are autophagic cell death markers. A pro-apoptotic molecule BAK is released from BAK/MCL-1 complex following GX15-070 treatment. Consistently, down-regulation of BAK reduces caspase-3 cleavage and cell death, but does not alter LC3 conversion. In contrast, down-regulation of ATG5, an autophagy regulator, decreases LC3 conversion and cell death, but does not alter caspase-3 cleavage, suggesting that apoptosis and autophagy induced by GX15-070 are independently regulated. Down-regulation of Beclin-1, which is capable of crosstalk between apoptosis and autophagy, affects GX15-070-induced cell death through apoptosis but not autophagy. Taken together, GX15-070 treatment in ALL could be an alternative regimen to overcome glucocorticoid resistance by inducing BAK-dependent apoptosis and ATG5-dependent autophagy. Enhanced anti-apoptotic BCL-2 family protein expression has been observed in several types of tumors. Targeting these proteins is therefore an attractive strategy for restoring the apoptosis process in tumor cells. Among the small molecule BCL-2 inhibitors, ABT-737 and its analog ABT-263 are the leading compounds currently in clinical development. However, these molecules have an affinity only with BCL-2 and BCL-XL, but not with MCL-1. Thus, ABT-737 can not be effective as a single agent therapeutic for ALL when MCL-1 is overexpressed. In contrast, GX15-070 can overcome the resistance conferred by high level of MCL-1. Our results suggest that GX15-070 could be useful as a single agent therapeutic against ALL and that the activity/expression of anti-apoptotic proteins could be a biomarker to determine the treatment strategy to ALL patients. (Supported by NIH R01CA134473 and the William Lawrence and Blanche Hughes Foundation) Disclosures: No relevant conflicts of interest to declare.

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