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Wu, Y.T., Zhang, S., Kim, Y.S., Tan, H.L., Whiteman, M., Ong, C.N., Liu, Z.G., Ichijo, H. and Shen, H.M. (2008) Signaling pathways from membrane lipid rafts to JNK1 activation in reactive nitrogen species-induced non-apo- ptotic cell death. Cell Death and Differentiation, 15, 386- 397. doi:10.1038/sj.cdd.4402273

has been cited by the following article:

• TITLE: Gentian extract induces caspase-independent and mitochondria-modulated cell death

  AUTHORS: Mika Ogata, Kazushige Matsukawa, Kiyomi Kogusuri, Tetsuro Yamashita, Takashi Hikage, Kikukatsu Ito, Yasushi Saitoh, Ken-ichi Tsutsumi

  KEYWORDS: Antiproliferative Activity; Cell Death; Mitochondria; Respiration; Gentiana Triflora

  JOURNAL NAME: Advances in Biological Chemistry, Vol.1 No.3, November 7, 2011

  ABSTRACT: 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 respira-tion. Consequently, different respiratory activities in mitochondria confer cells to have different suscepti-bilities to the extract-induced cell death.