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Adv Pharm Bull. 2020;10(1): 81-87.
doi: 10.15171/apb.2020.010
PMID: 32002365
PMCID: PMC6983994
Scopus ID: 85084199252
  Abstract View: 485
  PDF Download: 316

Research Article

Emerging Effects of Sepantronium Bromide (YM155) on MOLT-4 Cell Line Apoptosis Induction and Expression of Critical Genes Involved in Apoptotic Pathways

Kobra Shojaei Moghadam 1,2 ORCID logo, Majid Farshdousti Hagh 3, Mohammad Reza Alivand 4, Masoumeh Fardi 1,2 ORCID logo, Ali Akbar Movassaghpour 5, Ali Mohammadi 2,6, Maryam Moghadasi 1, Saeed Solali 7,8* ORCID logo

1 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4 Department of Medical Genetic, Tabriz University of Medical Sciences, Tabriz, Iran.
5 Hematology and Oncology Research Center, Tabriz University of medical Sciences, Tabriz, Iran.
6 Departments of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
7 Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
8 Division of Hematology and Transfusion Medicine, Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz.

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 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.

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.

Keywords: Apoptosis, Cancer, Drug, Survivin, MOLT-4, YM155
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Submitted: 27 Jun 2019
Revision: 08 Aug 2019
Accepted: 13 Aug 2019
ePublished: 11 Dec 2019
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