scholarly journals The Synergistic Effects of Decitabine Combined with Arsenic Trioxide (ATO) in the Human Myelodysplastic Syndrome Cell Line SKM-1

2016 ◽  
Vol 32 (4) ◽  
pp. 412-417 ◽  
Author(s):  
Ping Wu ◽  
Long Liu ◽  
Jianyu Weng ◽  
Suxia Geng ◽  
Chengxin Deng ◽  
...  
2016 ◽  
Vol 14 (5) ◽  
pp. 4180-4186 ◽  
Author(s):  
Hai-Ying Hua ◽  
Hua-Qiang Gao ◽  
Ai-Ning Sun ◽  
Jian-Nong Cen ◽  
Li-Li Wu

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4823-4823
Author(s):  
Fanyi Meng ◽  
Ming Huang

Abstract Abstract 4823 INTRODUCTION Proteĉ¢msome inhibitor bortezomib has used in treatment of hematology malignancies widely. We found it may reduce cell survival rate of HL60/ADR cell line and induce cell apoptosis in previous study. Now we are to investigate the effect of bortezomib alone or combined with arsenic trioxide (As2O3) on reversing multidrug resistance of HL60/ADR cell line and the possible machines. METHODS HL60/ADR cells were incubated with bortezomib at different doses alone and in combination with As2O3. The proliferation ratio was observed by MTT assay. Cell apoptosis was studied by fluorescence microscopy and flow cytometry. Intracellular concentration of daunorubicin (DNR) and multidrug resistance related protein-1 (MRP1) was determined by flow cytometry. P65Ap-p65Abcl-2AbaxAcaspase-3Acaspase-9APARP proteins were determined by western blot. RESULTS In bortezomib-treated tumor cells, inhibition rate increased in time- and dose-dependently, as well as apoptotic cells. Compared to bortezomib alone, combination with As2O3 inhibited the proliferation and induced the apoptosis of HL60/ADR cells more evident. Bortezomib can enhance the intraceflular accumulation of DNR and decrease MRP1 in HL60/ADM cells. The dual combination of As2O3 with bortezomib presents a superior anticancer and MRP1-decreased efficiency to either one of the drugs alone. Bortezomib can also elevate the expression of bax, caspase-3, caspase-9, PARP, and decelerate the expression of bcl-2, NF-κB p65, p-p65. CONCLUSIONS Bortezomib can reverse multidrug resistance of HL60/ADR cells and decrease the expression of MRP1 in cells. When combined with As2O3, it appears to synergistic effects. Its mechanisms might be associated with the inhibition of NF-κB activation, also with inhibiting anti-apoptosis proteins, boosting pro-apoptosis proteins, with followed activating caspase pathway. Disclosures: No relevant conflicts of interest to declare.


2019 ◽  
Vol 67 (7) ◽  
pp. 1067-1075 ◽  
Author(s):  
Lei Huang ◽  
Zhaoyun Liu ◽  
Huijuan Jiang ◽  
Lijuan Li ◽  
Rong Fu

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.


Author(s):  
Vahid CHANGIZI ◽  
Samayeh AZARIASL ◽  
Elahe MOTEVASELI ◽  
Saeedeh JAFARI NODOOSHAN

Background: Breast cancer is the most common invasive malignancy among women in the world. The current breast cancer therapies pose significant clinical challenges. Low-dose chemotherapy represents a new strategy to treat solid tumors in combination with natural products such as green tea catechins. Epigallocatechin-3-gallate (EGCG) is the major polyphenolic extract from green tea with potent anticancer and antioxidant effects. The purpose of this study was to investigate the effects of EGCG, Arsenic trioxide (ATO) and gamma radiation on MCF-7 cell line. Methods: The anti-proliferative effects of EGCG and ATO individually, moreover in combination with radiation on MCF-7 cells were evaluated with MTT assay. The expression of apoptotic gens (Bax, Bcl-2, Caspase-3 and Fas) was assessed by real-time PCR. Results: Based on the results of MTT assay, EGCG and ATO exhibited dose and time-dependent antiproliferative effects on MCF-7 cells. The combined therapy of EGCG and ATO in presence and absence radiation could rise cell death up to 80%. Moreover, integrated therapy made Bax up-regulated and Bcl-2 downregulated. Conclusion: In assessment synergistic effects of integrated therapy with EGCG and ATO and irradiation had been significant impact on low dose chemotherapy for breast cancer treatment.


2011 ◽  
Vol 37 (2) ◽  
pp. 370-380 ◽  
Author(s):  
Majid Zaki Dizaji ◽  
Mohsen Malehmir ◽  
Ardeshir Ghavamzadeh ◽  
Kamran Alimoghaddam ◽  
Seyed H. Ghaffari

2014 ◽  
Vol 8 (1) ◽  
pp. 85-90 ◽  
Author(s):  
LING-YUN ZHOU ◽  
FANG-YUAN CHEN ◽  
LI-JING SHEN ◽  
HAI-XIA WAN ◽  
JI-HUA ZHONG
Keyword(s):  

2016 ◽  
Vol 27 (suppl_9) ◽  
Author(s):  
A. Fani-Pakdel ◽  
S.H. Forouzmand ◽  
S.H. Mousavi ◽  
V. Vazifedan ◽  
M. Nourbakhsh ◽  
...  

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1665-1672
Author(s):  
TM McCarty ◽  
S Rajaraman ◽  
FF Elder ◽  
P Gadson ◽  
EB Thompson

A new hematopoietic cell line derived from a patient with Philadelphia chromosome (Ph1)-negative myeloblastic leukemia arising from a form of myelodysplastic syndrome (MDS) is described. This cell line, designated TMM, consists of immature cells with the morphological characteristics of young myeloblasts and grows in suspension culture with a doubling time of about 30 hours. By cytochemical analysis the cultured cells were positive for acid phosphatase. They were free of the Epstein-Barr virus-associated nuclear antigen as well as terminal deoxynucleotidyl transferase. Further phenotypic analysis revealed the expression of the myelomonocytic-specific antigen Leu-M1 and receptors for the Fc portion of IgG. Partial differentiation of these cells could be induced by dimethyl sulfoxide, tetradecanoyl phorbol acetate, or hypoxanthine and resulted in cells of the myeloid series expressing lysozyme and receptors for the C3b complement protein. The karyotype was 46,XY, lacked the Ph1 chromosome, and displayed no abnormalities at the light microscopic level. No rearrangement of the bcr-c-abl gene complex was found. This cell line should be useful for studying an important type of the heterogeneous population constituting Ph1-negative myeloblastic leukemia, arising in this instance from MDS, as well as for studying differentiation and proliferation of human pluripotent stem cells.


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