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Int J Mol Sci. 2010;11(12):4916-31. doi: 10.3390/ijms11124916. Epub 2010 Dec 1.

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.

Author information

1
Department of Microbiology and Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea; E-Mails: inkyeong@korea.ac.kr (I.K.L.); kbumjoon@snu.ac.kr (B.J.K.).

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 (Δψ(m)). Loss of the Δψ(m) 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 NH(2)-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.

KEYWORDS:

Compound K; c-Jun NH2-terminal kinase; mitochondrial membrane potential; p38 mitogen-activated protein kinase; reactive oxygen species

PMID:
21614182
PMCID:
PMC3100836
DOI:
10.3390/ijms11124916
[Indexed for MEDLINE]
Free PMC Article

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