Although there was an increase in the expression

of p-Akt protein in cells treated with bostrycin for 12 hours, when compared with cells at the 0 hour time selleck kinase inhibitor point, we showed a gradual decrease in p-Akt levels over time, with the most obvious reduction at 48 hours. We also showed a time-dependent increase in the levels of p27 protein in bostrycin-treated cells (Figure 4). Figure 4 Effects of Bostrycin on intracellular expression of p110α, p-Akt and p27 in A549 cells. A549 cells were treated with 10 mol/L bostrycin for 12, 24, 48, or 72 hours. Cells were harvested, total proteins were extracted and immunoblotted for p110α, p-Akt and p27. Untreated A549 cells were used as a control. Beta-actin was used as loading control. Discussion In this study, we demonstrated that bostrycin, a novel compound isolated from marine fungi in the South China Sea, GDC-0994 solubility dmso inhibited cell proliferation, blocked cell cycle progression, and promoted apoptosis of lung cancer A549 cells. Our data also suggested that the PI3K/AKT signaling pathway may play a role in bostrycin-mediated

inhibition of cell proliferation. Although bostrycin was previously shown to effectively inhibit cell growth and promote apoptosis in prostate cancer and gastric cancer [3, 4], it has not been used in lung cancer cells. To our knowledge, ours is the first study demonstrating that bostrycin significantly inhibited the growth of A549 cells in a concentration- and time-dependent Rucaparib manner. Regulation of the cell cycle and apoptosis is find more a major determinant dictating the development and progression of a number of cancers. PI3K/AKT inhibitors such as Tipifarnib, cause cell cycle arrest at the G1 or G2/M phase and induce apoptosis of human lung cancer

cells [5, 6] Our data were consistent with this study and showed that bostrycin treatment induced downregulation of PI3K/AKT signal pathway proteins, caused G0/G1 cell cycle arrest and promoted apoptosis in A549 cells. PI3K is composed of a p110αsubunit and p85 subunit and the PI3K/AKT signaling pathway has been shown to play a role in the development and progression of lung cancer [7]. Increased Akt activity has been reported in the bronchial endothelial cells of long-term smokers [8, 9] and persistently high levels of activated Akt was shown in bronchial endothelial cells from malignant tumors or precancerous lesions. Akt activation is thought to be related to poor prognosis of patients with lung cancer [10–12] and may be an important molecular target for treatment of lung cancer. The PI3K/AKT signaling pathway inhibits apoptosis by inactivating important members of the apoptotic cascade, including caspase-9, forkhead, and proapoptotic Bad [13–15] and by upregulating the transcription and translation of antiapoptotic genes via NFκB [16] and cell cycle genes like cyclin D1 and p27 [17].