Role of Valdien in proliferation and apoptosis of human non-Hodgkin's lymphoma cells in vitro

The aim of this study was to investigate the apoptosis of human non-Hodgkin lymphoma Namalwa cells induced by Valdien (N1, N3-bis (3-methoxysalicylidene) diethylenetriamine) and possible underlying mechanisms. Namalwa cells were cultured in vitro. MTT assay was used to observe the proliferation of Namalwa cells induced on Valdien. Annexin V-FITC/PE staining was used to quantify the percentages of apoptosis in the total cell population. Protein expression of cleaved caspase-3, caspase-9, Bcl-2, and Bax was investigated by Western blotting. Phosphoinositide 3 kinase (PI3K)/Akt signaling pathways were also examined. PI3K inhibitor LY294002 was used to examine the involvement of PI3K/Akt signaling pathways in this apoptosis-inducing effect. Results showed that Valdien (2.5-40 mu g/mL) markedly inhibited the proliferation of Namalwa cells and induced apoptosis in vitro. Valdien significantly increased the protein expression of cleaved caspase-9, caspase-3, and Bax, whereas it inhibited protein expression of Bcl-2 in the Valdien treatment group. In addition, Valdien significantly elevated levels of cytochrome c in cytosol. Further analysis demonstrated that Valdien-induced apoptosis was related to the inhibition of PI3K expression, which inactivated the phosphorylation of Akt. This phenomenon could be inhibited by the PI3K inhibitor LY294002. Thus, Valdien induced apoptosis in Namalwa cells through mitochondria-mediated and caspase-dependent pathways. Moreover, Valdien may induce the growth arrest and apoptosis of Namalwa cells through inhibiting PI3K/Akt signaling pathways.