Visit our Expo - Redox and Inflammation signaling 2012

Session III : Protein kinase cascades as therapeutic targets Poster III, 66
Inhibition of gap junction intercellular communication by capsaicin in rat liver
epithelial cells are mediated by phosphorylation of Cx43 and activation of ERK1/2
through activation of NADPH oxidase
Ji Hyuck Yim, Ki Won Lee, Jung Yeon Kwon, and Hyong Joo Lee*
Department of Food Biotechnology, School of Agricultural Biotechnology, and
Center for Agricultural Biomaterials, Seoul National University, Seoul 151-742,
Republic of Korea
Many studies have focused on the antimutagenic or anticarcinogenic activities of capsaicin
(trans-8-methyl-N-vanillyl-6-nonenamide) which is a major pungent ingredient in red pepper.
Recently, several studies have shown that anticarcinogenic effects of capsaicin may be partly
involved in the induction of apoptosis in several cancer cell lines. A recent study suggests that
the mechanism that makes antiproliferative activity of capsaicin in a human hepatocarcinoma
cells is due to their ability to produce hydrogen peroxide (H2O2) via activation of NADPH
oxidase. However, it can be argued that such inappropriate H2O2 generation may also have a
deleterious effect on nonmalignant cells as well. The present study investigated whether
capsaicin generates H2O2 at the intracellular levels and, if so, whether the formation of H2O2
by capsaicin induces carcinogenicity in normal rat liver epithelial cells. Capsaicin at the
concentration of 50µM completely inhibited gap junction intercellular communication (GJIC;
a carcinogenic phenomenon) in WB-F344 normal rat liver epithelial cells (WB cells) in a
dose-dependant manner. The inhibition of GJIC by capsaicin was mediated by
hyperphosphorylation of connexin 43 (Cx43) and activation of extracellular-regulated kinase
1/2 (ERK1/2) as demonstrated using pharmacological inhibitors of ERK1/2. Pretreatment of
WB cells with catalase and inhibitors of NADPH oxidase significantly reversed capsaicininduced
inhibition of GJIC and hyperphosphorylation of Cx43, suggesting that ROS may
mediate the inhibition of GJIC induced by capsaicin. These results indicate that the
antiproliferative effects of capsaicin on cancer cells are partially due to their prooxidant
actions, thereby indicating their potential toxicity and carcinogenicity.
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