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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Oncol+Rep
2016 ; 36
(3
): 1233-42
Nephropedia Template TP
gab.com Text
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English Wikipedia
Curcumin reduces the expression of survivin, leading to enhancement of arsenic
trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like
cells
#MMPMID27430728
Zeng Y
; Weng G
; Fan J
; Li Z
; Wu J
; Li Y
; Zheng R
; Xia P
; Guo K
Oncol Rep
2016[Sep]; 36
(3
): 1233-42
PMID27430728
show ga
Low response, treatment-related complications and relapse due to the low
sensitivity of myelodysplastic syndrome (MDS) and leukemia stem cells (LSCs) or
pre?LSCs to arsenic trioxide (ATO), represent the main problems following
treatment with ATO alone in patients with MDS. To solve these problems, a
chemosensitization agent can be applied to increase the susceptibility of these
cells to ATO. Curcumin (CUR), which possesses a wide range of anticancer
activities, is a commonly used chemosensitization agent for various types of
tumors, including hematopoietic malignancies. In the present study, we
investigated the cytotoxic effects and potential mechanisms in MDS-SKM-1 and
leukemia stem-like KG1a cells treated with CUR and ATO alone or in combination.
CUR and ATO exhibited growth inhibition detected by MTT assays and apoptosis
analyzed by Annexin V/PI analyses in both SKM-1 and KG1a cells. Apoptosis of
SKM-1 and KG1a cells determined by Annexin V/PI was significantly enhanced in the
combination groups compared with the groups treated with either agent alone.
Further evaluation was performed by western blotting for two hallmark markers of
apoptosis, caspase-3 and cleaved-PARP. Co-treatment of the cells with CUR and ATO
resulted in significant synergistic effects. In SKM-1 and KG1a cells, 31 and
13 proteins analyzed by protein array assays were modulated, respectively.
Notably, survivin protein expression levels were downregulated in both cell lines
treated with CUR alone and in combination with ATO, particularly in the latter
case. Susceptibility to apoptosis was significantly increased in SKM-1 and KG1a
cells treated with siRNA-survivin and ATO. These results suggested that CUR
increased the sensitivity of SKM-1 and KG1a cells to ATO by downregulating the
expression of survivin.
|Apoptosis/*drug effects
[MESH]
|Arsenic Trioxide
[MESH]
|Arsenicals/*pharmacology
[MESH]
|Caspase 3/metabolism
[MESH]
|Cell Line, Tumor
[MESH]
|Curcumin/*pharmacology
[MESH]
|Down-Regulation/drug effects
[MESH]
|Drug Synergism
[MESH]
|Humans
[MESH]
|Inhibitor of Apoptosis Proteins/*metabolism
[MESH]