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

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.