Int. J. Mol. Sci. 2010, 11(12), 4916-4931; doi:10.3390/ijms11124916
Article

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

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Received: 30 October 2010; in revised form: 19 November 2010 / Accepted: 19 November 2010 / Published: 1 December 2010
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 (IC50) 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.
Keywords: Compound K; reactive oxygen species; mitochondrial membrane potential; c-Jun NH2-terminal kinase; p38 mitogen-activated protein kinase
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MDPI and ACS Style

Lee, I.K.; Kang, K.A.; Lim, C.M.; Kim, K.C.; Kim, H.S.; Kim, D.H.; Kim, B.J.; Chang, W.Y.; Choi, J.H.; Hyun, J.W. 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. Int. J. Mol. Sci. 2010, 11, 4916-4931.

AMA Style

Lee IK, Kang KA, Lim CM, Kim KC, Kim HS, Kim DH, Kim BJ, Chang WY, Choi JH, Hyun JW. 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. International Journal of Molecular Sciences. 2010; 11(12):4916-4931.

Chicago/Turabian Style

Lee, In Kyung; Kang, Kyoung Ah; Lim, Chae Moon; Kim, Ki Cheon; Kim, Hee Sun; Kim, Dong Hyun; Kim, Bum Joon; Chang, Weon Young; Choi, Jae Hyuck; Hyun, Jin Won. 2010. "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." Int. J. Mol. Sci. 11, no. 12: 4916-4931.


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