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

In Kyung Lee 1 email, Kyoung Ah Kang 2 email, Chae Moon Lim 2 email, Ki Cheon Kim 2 email, Hee Sun Kim 3 email, Dong Hyun Kim 4 email, Bum Joon Kim 1 email, Weon Young Chang 2 email, Jae Hyuck Choi 2,* email and Jin Won Hyun 2,* email
1 Department of Microbiology and Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea 2 School of Medicine, Jeju National University, Jeju 690-756, Korea 3 Department of Neuroscience, College of Medicine, Ewha Womans University, Seoul 110-783, Korea 4 Department of Microbial Chemistry, College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea
* Authors to whom correspondence should be addressed.
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)
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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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Cite This Article

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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