Virosecurinine induces apoptosis in human leukemia THP‑1 cells and other underlying molecular mechanisms

Zhang,Gang; Gao,Xiaohui; Zeng,Hui; Li,Yuan; Guo,Xiaojun

doi:10.3892/ol.2017.7437

Virosecurinine induces apoptosis in human leukemia THP‑1 cells and other underlying molecular mechanisms

Authors:
- Gang Zhang
- Xiaohui Gao
- Hui Zeng
- Yuan Li
- Xiaojun Guo
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Affiliations: Department of Hematology, First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China, Department of Pediatrics, First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
Published online on: November 17, 2017 https://doi.org/10.3892/ol.2017.7437
Pages: 849-854
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Virosecurinine, a primary alkaloid from Securinega suffruticosa plant is known as a potent differentiation‑inducing agent in acute leukemia cells. The present study aimed to investigate the effects and underlying mechanisms of virosecurinine on human leukemia THP‑1 cells in vitro. The effects of virosecurinine on cell proliferation were assessed by CCK‑8. The effects on apoptosis and cell cycle were assessed by staining with annexin V‑fluorescein isothiocyanate and propidium iodide, respectively followed by flow cytometric analysis. The apoptotic cell bodies were observed using a transmission electron microscope, while the mRNA expression of phosphoinositide 3‑kinase (PI3K), protein kinase B (AKT), mechanistic target of rapamycin (mTOR) and phosphatase and tensin homolog (PTEN) in THP‑1 was evaluated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Treatment with virosecurinine was able to decrease the viability of THP‑1 cells in a dose‑ and time‑dependent manner. The IC50 values of virosecurinine at 24, 48, and 72 h post‑treatment were 68.128, 23.615, and 13.423 µmol/l, respectively. Cell cycle was arrested at the G1/S phase in virosecurinine‑treated cells; however, not in untreated control cells. Numerous apoptotic bodies were observed in the THP‑1 cells, which were treated with 12.5 µmol/l virosecurinine for 48 h. RT‑qPCR indicated that treatment with virosecurinine resulted in upregulated PTEN expression and downregulated expression of PI3K, AKT and mTOR in THP‑1 cells. The present study demonstrated that treatment with virosecurinine was able to inhibit proliferation and induce apoptosis in THP‑1cells by exerting an inhibitory effect on the activation of PI3K/AKT/mTOR signaling pathways. Therefore, our data suggested that virosecurinine is a promising anti‑tumor agent for the treatment of acute monocytic leukemia.

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