Autophagy Inhibition Potentiates the Anticancer Effects of a Bendamustine Derivative NL-101 in Acute T Lymphocytic Leukemia
Joint Authors
Gao, Hang
Lou, Siyue
Hong, Huanwu
Ge, Qiufu
Zhao, Huajun
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-02-14
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Acute T lymphocytic leukemia (T-ALL) is an aggressive hematologic resulting from the malignant transformation of T-cell progenitors.
Drug resistance and relapse are major difficulties in the treatment of T-ALL.
Here, we report the antitumor potency of NL-101, a compound that combines the nitrogen mustard group of bendamustine with the hydroxamic acid group of vorinostat.
We found NL-101 exhibited efficient antiproliferative activity in T-ALL cell lines (IC50 1.59–1.89 μM), accompanied by cell cycle arrest and apoptosis, as evidenced by the increased expression of Cyclin E1, CDK2, and CDK4 proteins and cleavage of PARP.
In addition, this bendamustine-derived drug showed both a HDACi effect as demonstrated by histone hyperacetylation and p21 transcription and a DNA-damaging effect as shown by an increase in γ-H2AX.
Intriguingly, we found that NL-101-induced autophagy in T-ALL cells through inhibiting Akt-mTOR signaling pathway, as indicated by an increase in LC3-I to LC3-II conversion and decrease of p62.
Furthermore, inhibition of autophagy by 3-methyladenine increased apoptotic cell death by NL-101, suggesting a prosurvival role of autophagy.
In summary, our finding provides rationale for investigation of NL-101 as a DNA/HDAC dual targeting drug in T-ALL, either as a single agent or in combination with autophagy inhibitors.
American Psychological Association (APA)
Gao, Hang& Lou, Siyue& Hong, Huanwu& Ge, Qiufu& Zhao, Huajun. 2020. Autophagy Inhibition Potentiates the Anticancer Effects of a Bendamustine Derivative NL-101 in Acute T Lymphocytic Leukemia. BioMed Research International،Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1131701
Modern Language Association (MLA)
Gao, Hang…[et al.]. Autophagy Inhibition Potentiates the Anticancer Effects of a Bendamustine Derivative NL-101 in Acute T Lymphocytic Leukemia. BioMed Research International No. 2020 (2020), pp.1-12.
https://search.emarefa.net/detail/BIM-1131701
American Medical Association (AMA)
Gao, Hang& Lou, Siyue& Hong, Huanwu& Ge, Qiufu& Zhao, Huajun. Autophagy Inhibition Potentiates the Anticancer Effects of a Bendamustine Derivative NL-101 in Acute T Lymphocytic Leukemia. BioMed Research International. 2020. Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1131701
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1131701