Euphorbia angustifolia lactone B inhibits A549 proliferation and induces apoptosis

The study is to investigate the effect of Euphorbia angustifolia lactone B (Jolkinolide B, JB) on the proliferation and apoptosis of A549 cells. The proliferation of A549 cells was detected by tetramethyl azothiolide. Activity changes of intracellular caspase-3, 8, 9 were determined by spectrophotometry. The content of cytochrome C (Cyt C) protein and the expression quantity of Bcl-2, Bax, p-ERK1/2, and p-Akt proteins were detected by Western blot and the apoptosis rates were detected by flow cytometry. JB significantly inhibited cell proliferation in a time-dose manner. With increase in JB concentrations, the expression level of Bax protein greatly increased, and the expression of caspase-3 and caspase-9 significantly increased with significant difference (P<0.01). Besides, the peak value of mitochondrial membrane potential decreased, while the number of cells distributed in the depolarized region increased, which was different from that in the control (P<0.05). Moreover, the expression levels of p-ERK1/2 and p-Akt in A549 cells gradually decreased with extending exposure duration. Moreover, 20 μ mol/L LY294002 (an PI3K inhibitor) + 120μg/mL JB and 10μmol/L PD98059 (an ERK inhibitor) +120μg/mL JB also increased apoptosis rates of A549 cells. JB could induced cell apoptosis through promoting endogenous mitochondrial signal transduction pathway and inhibiting PI3K/ERK pathway.