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

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 G 2 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. By screening a natural compound library owned by State Key Laboratory of Quality Research in Chinese Medicine (Macau, China), it was revealed that hirsutanol A exerted a clear inhibitory effect on the viability of the T-ALL cell line Jurkat. Hirsutanol A is a sesquiterpenoid compound initially

Aloe‐emodin targets multiple signaling pathways by blocking ubiquitin‐mediated degradation of DUSP1 in nasopharyngeal carcinoma cells

“…For quantitative analysis of cell cycle phases, a Cell Cycle Detection Kit (Life‐iLab Biotech, Shanghai, China) was used and the cells were incubated with 10 μM AE for 48 h, digested, collected in 70% ethanol at −20°C, and fixed for 2 h. Fixed cells were centrifuged at ×1000 g and washed with ice‐cold PBS, resuspended in staining buffer (0.5 ml) containing PI (25 μl) and RNase A (10 μl), and incubated at 37°C for 30 min in the dark. Finally, DNA content was measured via FCM (Zhong et al, 2021).…”

FERMT1 contributes to the progression of prostate cancer through the p53 pathway

“…5A). Notably, the p53 pathway is a vital signaling pathway in tumor biology 23 , and p53 saves as one of the master regulators of cell proliferation and cell death 24 . Herein, the downregulation of FERMT1 enhanced the expression of the apoptosis-related protein p53, and this effect could be signi cantly reversed by pretreatment with PFTα (Fig.…”