Visit our Expo - Redox and Inflammation signaling 2012

Session III : Protein kinase cascades as therapeutic targets Poster III, 44
Differential modulation of AMPK signaling pathways by low or high levels of exogenous
reactive oxygen species in colon cancer cells
In-Ja Park, Jin-Taek Hwang 1 , Young Min Kim 2 , Joohun Ha 1 and Ock Jin Park
Department of Food and Nutrition, Hannam University, 133 Ojeong-dong Daedeok-gu,
Daejeon 306-791, Korea, E-mail: ojpark@hannam.ac.kr
1 Department of Biochemistry and Molecular Biology, Medical Research Center for
Bioreaction to Reactive Oxygen Species, Kyung Hee University College of Medicine,
Seoul 130-791, Korea
2 Department of Biological Sciences, Hannam University, Daejeon 306-791, Korea
ROS have been regarded as undesirable metabolic byproducts often linked to macromolecule
damage, aging or degenerative diseases. However, ROS emerge as important intracellular
signaling molecules, which act as mediators or second messengers at nontoxic concentrations
through receptor-transducing pathways. In cancer cell system, ROS exert a paradoxical effect.
ROS can promote tumor growth by transforming normal cells through activation of
transcription factors or inhibition of tumor suppressor genes, whereas the elevated levels
would inhibit tumor cells through the stimulation of proapoptotic-signals. The excess ROS
generate cell cycle arrest and apoptotic cell death or even necrosis in severe cases. Therefore,
the maintenance of ROS homeostasis is extremely important to cell signaling and the
regulation of cell death.
The present study was undertaken to examine the effect of low and high concentrations of
H 2O 2 on cancer cell proliferation and apoptosis, and AMPK signaling pathways in HT-29
human colon cancer cells. Non-toxic dose of H 2O 2 (10 uM) induced cancer cell proliferation,
whereas the toxic level of 1000 uM H 2O 2 induced apoptosis. The stimulation of cell
proliferation was accompanied with an increase in cyclooxygenase-2 (COX-2), and apoptosis
induced by high-dose H 2O 2 was correlated with the activation of AMPK and negatively
correlated with COX-2 expression. These results suggest that ROS at non-toxic levels can
stimulate cancer cell growth by regulating AMP-activated protein kinase (AMPK) and/or
COX-2, and the abundant exogenous ROS linked to the growth inhibition through modulating
AMPK signaling pathways.
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