Hirsutanol A inhibits T-acute lymphocytic leukemia Jurkat cell viability through cell cycle arrest and p53-dependent induction of apoptosis.

Content Provider	Europe PMC
Author	Zhong, Fangfang Yang, You Ren, Danwei Long, Sili Qin, Xiang Liu, Jing Zeng, Yan Lan, Wenjian Ma, Wenzhe Liu, Wenjun
Copyright Year	2020
Abstract	Acute lymphocytic leukemia (ALL) is a type of childhood leukemia with the highest incidence; T-acute lymphocytic leukemia (T-ALL) is far more difficult to treat than B-acute lymphocytic leukemia (B-ALL) and has a poor long-term prognosis. Therefore, there is an urgent requirement to develop effective drugs for the treatment of T-ALL. Hirsutanol A is a natural sesquiterpenoid compound. The aim of the present study was to evaluate the in vitro anticancer activity of hirsutanol A against T-acute lymphocytic leukemia Jurkat cells and investigate the mechanism of action. A Cell Counting Kit-8 assay demonstrated that hirsutanol A inhibited the viability of Jurkat cells in a dose- and time-dependent manner. In addition, hirsutanol A induced cell cycle arrest at the G2 phase as determined via flow cytometry. Furthermore, Hoechst staining, Annexin V-FITC/propidium iodide double staining, mitochondrial membrane potential detection using JC-1 and western blot analysis of apoptotic proteins indicated that the inhibitory effect of hirsutanol A on Jurkat cells was associated with the induction of apoptosis. Of note, hirsutanol A induced the expression of the tumor suppressor p53, whereas simultaneous treatment with pifithrin-α, an inhibitor of p53, significantly reduced Jurkat cell apoptosis induced by hirsutanol A. In summary, the present study suggested that hirsutanol A inhibited Jurkat cell viability through induction of cell cycle arrest and p53-dependent initiation of apoptosis, thus hirsutanol may serve as a promising compound for the treatment of T-ALL.
ISSN	17920981
Journal	Experimental and Therapeutic Medicine
Volume Number	22
PubMed Central reference number	PMC8138276
Issue Number	1
PubMed reference number	34055057
e-ISSN	17921015
DOI	10.3892/etm.2021.10173
Language	English
Publisher	D.A. Spandidos
Publisher Date	2021-05-11
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Zhong et al.
Subject Keyword	hirsutanol A apoptosis T-acute lymphocytic leukemia p53
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Cancer Research