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Emerging Effects of Sepantronium Bromide (YM155) on MOLT-4 Cell Line Apoptosis Induction and Expression of Critical Genes Involved in Apoptotic Pathways.
- Source :
- Advanced Pharmaceutical Bulletin; 2020, Vol. 10 Issue 1, p81-87, 7p
- Publication Year :
- 2020
-
Abstract
- Purpose: Sepantronium bromide (YM155) is a Survivin inhibitor which recently advanced as an anticancer agent in phase II clinical trials. Survivin belongs to IAP (inhibitor of apoptosis) gene family and is a pivotal target for treatment due to its over expression and oncogenic function in many malignancies, including acute lymphoblastic leukemia (ALL). Although survivin is a specific target for YM155, recent reports have shown that it has many other crucial targets that regulate its anti-apoptotic effects. The aim of this study was to investigate whether YM155 could have an effect on cell death-inducing genes as well as inducing apoptosis in T-ALL MOLT4-cell line. Methods: We treated MOLT-4 cells with increasing concentrations of YM155 and then cell viability was determined using MTT (methyl thiazolyl tetrazolium) assay. Also, the rate of induction of apoptosis in MOLT-4 cells and the target genes expression levels were evaluated by Annexin V/PI and real-time PCR, respectively. Results: YM155 inhibited cell growth in MOLT-4 cells. This outcome is achieved by inducing apoptosis and a significant increase in the expression level of P53, MiR-9, caspase 3 and decreasing the mRNA expression levels of survivin, Sirtuin1(SIRT1), member of anti-apoptotic proteins family (Bcl-2), and epithelial-to-mesenchymal transition (EMT) initiating factors Snail1and Zeb2. Conclusion: The results showed that use of YM155 can be a potential drug therapy in T-ALL patients with promising effects on apoptosis induction. [ABSTRACT FROM AUTHOR]
- Subjects :
- CELL lines
LYMPHOBLASTIC leukemia
GENE families
BROMIDES
ACUTE leukemia
Subjects
Details
- Language :
- English
- ISSN :
- 22285881
- Volume :
- 10
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Advanced Pharmaceutical Bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 140992906
- Full Text :
- https://doi.org/10.15171/apb.2020.010