XXXX selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs- @entity3726 .

@entity1477 @entity146 @entity5 @entity3726 @entity26 @entity3963 @entity67056 @entity7952 @entity4675 @entity1435 @entity157 @entity5593
UNASSIGNED: @entity157 ( @entity157 ) are highly malignant and @entity146 lack of effective therapeutic drugs. @entity67056 (PL), a natural product isolated from longer pepper plants, is recently identified as a potent cytotoxic compound highly selective to @entity5 cells. Here, we reported that PL specifically suppressed @entity157 cell migration/invasion via endoplasmic reticulum (ER)-MAPKs- @entity3726 signaling pathway. PL selectively killed @entity157 cells but not normal hepatocytes with an IC50 of 10-20   M while PL at much lower concentrations only suppressed @entity157 cell migration/invasion. PL selectively elevated reactive @entity26 species (ROS) in @entity157 cells, which activated or up-regulated downstream @entity7952 / @entity5593 / @entity1477 , @entity1435 / @entity4675 / @entity3963 and @entity3726 subsequently. Administration of antioxidants completely abolished PL's effects on cell death and migration/invasion. However, pharmacological inhibition of ER stress-responses or MAPKs signaling pathways with corresponding specific inhibitors only reversed PL's effect on cell migration/invasion but not on cell death. Consistently, knocking-down of @entity3726 by RNA interference only reversed PL-suppressed @entity157 cell migration. Finally, PL significantly suppressed @entity157 development and activated the ER-MAPKs- @entity3726 signaling pathway in @entity157 xenografts in vivo. Taken together, PL selectively killed @entity157 cells and preferentially inhibited @entity157 cell migration/invasion via ROS-ER-MAPKs- @entity3726 axis, suggesting a novel therapeutic strategy for the highly malignant and aggressive @entity157 clinically.
