AKT/mTOR signaling pathway is involved in salvianolic acid B-induced autophagy and apoptosis in hepatocellular carcinoma cells.

Chinese medicines are emerging as an attractive new generation of anticancer drugs. Here, we explored the impact of salvianolic acid B (Sal B), the major water-soluble compounds of Danshen, on apoptosis and autophagy of human hepatocellular carcinoma cells (HCC). We also investigated the related molecular mechanisms. We found that Sal B exhibits potent ability to inhibit HCC cells viability in a concentration-dependent manner, and to induce apoptosis via the mitochondrial apoptosis pathway. Additionally, Sal B could also induce autophagy. Furthermore, pretreatment with the autophagy inhibitor chloroquine or 3-methyladenine showed the potential in attenuating the apoptosis rate induced by Sal B. Mechanistically, Sal B treatment inhibited the AKT/mTOR signaling cascade in vitro. Overexpression of AKT abolished the effects of Sal B on HCC cells, suggesting a critical role of the AKT/mTOR signaling pathway in Sal B-induced biological effects. Our results indicated that the mitochondrial pathway was involved in Sal B-induced apoptosis of HCC cells. Moreover, the AKT/mTOR signaling pathway was involved in Sal B-induced autophagy, which promoted apoptosis. This study may provide a promising strategy for using Sal B as a chemotherapeutic agent for patients with HCC.

How an uncertain cue modulates subsequent monetary outcome evaluation: an ERP study.

People avert uncertain situations more than certain ones, and the neural correlates of such acts have gained increasing attention in past decade. However, the electrophysiological bases of how subjects respond to uncertain cues, and how such cues affect subsequent outcome evaluations have rarely been explored. In the present study, participants completed a gambling task while their neural activities were recorded through electroencephalography. The results indicated that subjects were sensitive to the uncertain cue as represented by feedback-related negativity (FRN). This uncertain cue further enhanced the neural response to outcome evaluation represented by P200, FRN, and P300 temporally. The enhanced P200 outcome may reflect the negative bias of the emotional reaction, which is a reflection of uncertain deviation at an early stage. The discrepancies of differentiated feedback-related negativity between uncertain and certain condition indicated increased motivation or prediction error toward the outcome. Finally, the increased P300 amplitude under uncertain outcome compared with certain one, as well as its sensitivity to the valence of the outcome under uncertain condition, embodies the increased arousal of the affective response. Therefore, uncertain cue effects observed in the current study suggest that uncertainty induces a larger motivational/affective and expectation response toward outcome revelation.