Compound K, a metabolite of ginseng saponin, induces mitochondria-dependent and caspase-dependent apoptosis via the generation of reactive oxygen species in human colon cancer cells

In Kyung Lee, Kyoung Ah Kang, Chae Moon Lim, Ki Cheon Kim, Hee Sun Kim, Dong Hyun Kim, Bum Joon Kim, Weon Young Chang, Jae Hyuck Choi, Jin Won Hyun

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

The objective of this study was to elucidate the cytotoxic mechanism of Compound K, with respect to the involvement of reactive oxygen species (ROS) and the mitochondrial involved apoptosis, in HT-29 human colon cancer cells. Compound K exhibited a concentration of 50% growth inhibition (IC 50) at 20 μg/mL and cytotoxicity in a time dependent manner. Compound K produced intracellular ROS in a time dependent fashion; however, N-acetylcysteine (NAC) pretreatment resulted in the inhibition of this effect and the recovery of cell viability. Compound K induced a mitochondria-dependent apoptotic pathway via the modulation of Bax and Bcl-2 expressions, resulting in the disruption of the mitochondrial membrane potential (ΔΨm). Loss of the ΔΨm was followed by cytochrome c release from the mitochondria, resulting in the activation of caspase-9, -3, and concomitant poly ADP-ribosyl polymerase (PARP) cleavage, which are the indicators of caspase-dependent apoptosis. The apoptotic effect of Compound K, exerted via the activation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), was abrogated by specific MAPK inhibitors. This study demonstrated that Compound K-mediated generation of ROS led to apoptosis through the modulation of a mitochondria-dependent apoptotic pathway and MAPK pathway.

Original languageEnglish
Pages (from-to)4916-4931
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume11
Issue number12
DOIs
StatePublished - Dec 2010

Keywords

  • Compound K
  • Mitochondrial membrane potential
  • Reactive oxygen species
  • c-Jun NH -terminal kinase
  • p38 mitogen-activated protein kinase

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