Gentian extract induces caspase-independent and mitochondria-modulated cell death

Extracts from the dried roots of gentian plant, Gentiana triflora, exhibit an antiproliferative activity against cultured and implanted tumor cells. However, the underlying mechanism has been unclear. In the present study, we show that the cell death induced by the extract occurs caspase-independently and depends on metabolic status of mitochondrial respiration. We observed that sensitivity to the extract was considerably lower in HeLa cells, which have a low rate of mitochondrial respiration, in comparison to Y3-Ag1.2.3 cells, which have a higher rate of respiration. Furthermore, sensitivity of HeLa cells to the extract increased significantly when they were forced to switch their energy dependency from glycolysis to mitochondrial respiration. These results indicate that the gentian extract targets on mitochondrial respiration. Consequently, different respiratory activities in mitochondria confer cells to have different susceptibilities to the extract-induced cell death.