Emerging Effects of Sepantronium Bromide (YM155) on MOLT-4 Cell Line Apoptosis Induction and Expression of Critical
Kobra Shojaei Moghadam1,2, Majid Farshdousti Hagh3, Mohammad Reza Alivand4
1Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Abstract:
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 overexpression 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. 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. 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. The results showed that use of YM155 can be a potential drug therapy in T-ALL patients with promising effects on apoptosis induction.
Insights
Sepantronium bromide (YM155) induces apoptosis and inhibits growth in T-cell acute lymphoblastic leukemia (T-ALL) cells. This survivin inhibitor shows potential as a therapeutic agent for T-ALL by modulating key cell death and survival genes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Survivin is overexpressed in malignancies like acute lymphoblastic leukemia (ALL), making it a key therapeutic target.
- Sepantronium bromide (YM155) is a survivin inhibitor investigated as an anticancer agent.
- YM155 may target additional pathways beyond survivin, influencing apoptosis.
Purpose of the Study:
- To investigate the effects of YM155 on apoptosis induction in T-ALL MOLT-4 cells.
- To determine if YM155 impacts cell death-inducing genes.
- To analyze the gene expression changes associated with YM155 treatment in T-ALL.
Main Methods:
- MOLT-4 cells were treated with varying concentrations of YM155.
- Cell viability was assessed using the MTT assay.
- Apoptosis induction was measured by Annexin V/PI staining, and gene expression was analyzed via real-time PCR.
Main Results:
- YM155 demonstrated significant inhibition of MOLT-4 cell growth.
- Apoptosis was induced in MOLT-4 cells treated with YM155.
- YM155 upregulated P53, MiR-9, and caspase 3, while downregulating survivin, SIRT1, Bcl-2, Snail1, and Zeb2 mRNA levels.
Conclusions:
- YM155 effectively inhibits T-ALL cell growth by inducing apoptosis.
- The drug modulates the expression of critical genes involved in apoptosis, cell survival, and EMT.
- YM155 presents a promising therapeutic strategy for T-cell acute lymphoblastic leukemia.
More Related Videos
09:18Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
07:47Apoptosis Induction and Detection in a Primary Culture of Sea Cucumber Intestinal Cells
Published on: January 21, 2020
