scholarly journals Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells

2016 ◽  
Vol 36 (3) ◽  
pp. 1233-1242 ◽  
Author(s):  
Yingjian Zeng ◽  
Guangyang Weng ◽  
Jiaxin Fan ◽  
Zhangqiu Li ◽  
Jianwei Wu ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Arsenic Trioxide ◽  
Induced Apoptosis

Decitabine shows synergistic effects with arsenic trioxide against myelodysplastic syndrome cells via endoplasmic reticulum stress-related apoptosis

2019 ◽  
Vol 67 (7) ◽  
pp. 1067-1075 ◽  
Author(s):  
Lei Huang ◽  
Zhaoyun Liu ◽  
Huijuan Jiang ◽  
Lijuan Li ◽  
Rong Fu
Keyword(s):  
Myelodysplastic Syndrome ◽  
Er Stress ◽  
Arsenic Trioxide ◽  
Function Analysis ◽  
Synergistic Effects ◽  
Single Agent ◽  
International Prognostic Scoring System ◽  
Combination Group ◽  
Stress Related Genes ◽  
Induced Apoptosis

Most of the International Prognostic Scoring System (IPSS) high-risk patients with myelodysplastic syndrome partly responded to hypomethylating therapy even with transient remission, while arsenic trioxide (ATO) had partial effect in patients with MDS. Therefore, we sought to investigate the effects and possible mechanisms of the combination of ATO and decitabine (DAC) in MDS cells. In our study, the MUTZ-1 and SKM-1 cells were treated with ATO, DAC or both. Cell viability, cell apoptosis, levels of reactive oxygen species (ROS) and expressions of the endoplasmicreticulum (ER) stress-associated genes and proteins were examined. Results showed the combination of ATO and DAC synergistically inhibited the proliferation and induced apoptosis of MDS cells. Through the RNA-sequence and GSEA gene function analysis, ER stress-related pathway played an important role in apoptosis of MDS cells induced by the combination of ATO and DAC. ER stress-related genes DNA damage inducible transcript 3, GRP78, and activating transcription factor-6 were significantly highly expressed in combination group than those in single agent groups; proteins were confirmed by western blot. The levels of ROS significantly increased in the combination group. Furthermore, the apoptosis of (ATO+DAC) group MDS cells could be partially reversed by antioxidant agent N-acetylcysteine, accompanied by decreased expression of intracellular ROS and ER stress-related genes. These results suggested that the combination of ATO and DAC synergistically induced the apoptosis of MDS cells by increased ROS-related ER stress in MDS cells.

EVI-1 modulates arsenic trioxide induced apoptosis through JNK signalling pathway in leukemia cells

2019 ◽  
Vol 374 (1) ◽  
pp. 140-151 ◽  
Author(s):  
Wenjing Lang ◽  
Jianyi Zhu ◽  
Fangyuan Chen ◽  
Jiayi Cai ◽  
Jihua Zhong
Keyword(s):  
Arsenic Trioxide ◽  
Signalling Pathway ◽  
Leukemia Cells ◽  
Induced Apoptosis

Arsenic Trioxide and Melarsoprol Induce Programmed Cell Death in Myeloid Leukemia Cell Lines and Function in a PML and PML-RAR Independent Manner

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1497-1504 ◽  
Author(s):  
Zhu-Gang Wang ◽  
Roberta Rivi ◽  
Laurent Delva ◽  
Andrea König ◽  
David A. Scheinberg ◽  
...  
Keyword(s):  
Cell Line ◽  
Arsenic Trioxide ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Leukemia Cell ◽  
Nuclear Bodies ◽  
Independent Manner ◽  
Leukemia Cell Lines ◽  
Induced Apoptosis ◽  
Myeloid Leukemia Cell

Abstract Inorganic arsenic trioxide (As2O3) and the organic arsenical, melarsoprol, were recently shown to inhibit growth and induce apoptosis in NB4 acute promyelocytic leukemia (APL) and chronic B-cell leukemia cell lines, respectively. As2O3 has been proposed to principally target PML and PML-RAR proteins in APL cells. We investigated the activity of As2O3 and melarsoprol in a broader context encompassing various myeloid leukemia cell lines, including the APL cell line NB4-306 (a retinoic acid–resistant cell line derived from NB4 that no longer expresses the intact PML-RAR fusion protein), HL60, KG-1, and the myelomonocytic cell line U937. To examine the role of PML in mediating arsenical activity, we also tested these agents using murine embryonic fibroblasts (MEFs) and bone marrow (BM) progenitors in which the PML gene had been inactivated by homologous recombination. Unexpectedly, we found that both compounds inhibited cell growth, induced apoptosis, and downregulated bcl-2 protein in all cell lines tested. Melarsoprol was more potent than As2O3 at equimolar concentrations ranging from 10−7 to 10−5 mol/L. As2O3 relocalized PML and PML-RAR onto nuclear bodies, which was followed by PML degradation in NB4 as well as in HL60 and U937 cell lines. Although melarsoprol was more potent in inhibiting growth and inducing apoptosis, it did not affect PML and/or PML-RAR nuclear localization. Moreover, both As2O3 and melarsoprol comparably inhibited growth and induced apoptosis of PML+/+ and PML−/− MEFs, and inhibited colony-forming unit erythroid (CFU-E) and CFU granulocyte-monocyte formation in BM cultures of PML+/+ and PML−/− progenitors. Together, these results show that As2O3 and melarsoprol inhibit growth and induce apoptosis independent of both PML and PML-RAR expression in a variety of myeloid leukemia cell lines, and suggest that these agents may be more broadly used for treatment of leukemias other than APL. © 1998 by The American Society of Hematology.

Arsenic trioxide, thalidomide and retinoid acid combination therapy in higher risk myelodysplastic syndrome patients

2008 ◽  
Vol 32 (2) ◽  
pp. 251-254 ◽  
Author(s):  
Wen-Li Zheng ◽  
Guang-Sen Zhang ◽  
Yun-Xiao Xu ◽  
Jian-Kai Shen ◽  
Chong-Wen Dai ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Myelodysplastic Syndrome ◽  
Arsenic Trioxide ◽  
Retinoid Acid

scholarly journals Arsenic trioxide and triptolide synergistically induce apoptosis in the SKM-1 human myelodysplastic syndrome cell line

2016 ◽  
Vol 14 (5) ◽  
pp. 4180-4186 ◽  
Author(s):  
Hai-Ying Hua ◽  
Hua-Qiang Gao ◽  
Ai-Ning Sun ◽  
Jian-Nong Cen ◽  
Li-Li Wu
Keyword(s):  
Myelodysplastic Syndrome ◽  
Cell Line ◽  
Arsenic Trioxide

Myeloperoxidase Is Required for the Combined Apoptotic Effects of Arsenic Trioxide with Ascorbic Acid or Epigallocatechin-3-Gallate in Myeloid Leukemia Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3474-3474
Author(s):  
Lijuan Xia ◽  
Min Lu ◽  
Duo Chen ◽  
Samuel Waxman ◽  
Yongkui Jing
Keyword(s):  
Ascorbic Acid ◽  
Nadph Oxidase ◽  
Arsenic Trioxide ◽  
Myeloid Leukemia ◽  
K562 Cells ◽  
H2o2 Production ◽  
Nb4 Cells ◽  
Combination Treatments ◽  
Induced Apoptosis ◽  
High Level

Abstract Arsenic trioxide (As2O3) is a drug used world-wide that selectively causes the death of acute promyelocytic leukemia (APL) cells by novel mechanisms and induces complete clinical remission in 90% of patients without significant toxicity. The outstanding success of As2O3 therapy in relapsed APL patients has not been replicated by an equivalent success in other types of acute myeloid leukemia (AML). We have studied As2O3 mechanism(s) of action and identified agents to use in combination to improve the use of As2O3 as a treatment for other types of AML. As2O3 produces higher levels of H2O2 and apoptosis in APL NB4 cells than in other AML cells at therapeutic concentrations of 1-2 uM. As2O3 does not induce apoptosis in HL-60 cells but is synergistic with ascorbic acid (AA) or epigallocatechin-3-gallate (EGCG). Both AA and EGCG produce H2O2 which is augmented by the addition of As2O3. Apoptosis induction by As2O3 in combination with AA or EGCG is inhibited by catalase and the antioxidant N-acetylcysteine. Myeloperoxidase (MPO), a major neutrophil enzyme, augments H2O2-induced apoptosis by converting it into more potent reactive oxygen species. HL-60, NB4, SKNO-1 and PLB985 cells which express high level of MPO, but not U937 and K562 cells without expression of MPO, are responsive to As2O3 plus AA or EGCG-induced apoptosis. HP-100 cells, a subclone of HL-60 cells without MPO expression, are resistant to both combination treatments. MPO stable transfection sensitizes K562 cells to apoptosis following treatment with As2O3 and AA or EGCG. NADPH oxidase is an enzyme complex which generates O2− and H2O2 in neutrophils. In APL NB4 cells, As2O3 induces expression of NADPH oxidase members and is thought to participate in H2O2 production required for As2O3 response. X-CGD cells, a subclone of PLB-985 with targeted disruption of the gp91phox gene (Zhen et al, PNAS90:9832, 1993) and loss of NADPH oxidase activity but with high levels of MPO activity, are responsive to treatment with As2O3 and AA or EGCG. These results suggest that AA and EGCG enhance As2O3-induced apoptosis through a synergistic production of H2O2 which is independent NADPH oxidase activation in non-APL AML cells. MPO augments the apoptotic effect of H2O2 produced by As2O3 plus AA or EGCG and it could be used as a marker to predict the sensitivity of AML cells to both combination treatments.

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