Chemopreventive effect of punicalagin, a novel tannin component isolated from Terminalia catappa, on H-ras-transformed NIH3T3 cells

Terminalia catappa and its major tannin component, punicalagin, have been characterized to possess antioxidative and antigenotoxic activities. However, their effects on reactive oxygen species (ROS) mediated carcinogenesis are still unclear. In the present study, H-ras-transformed NIH3T3 cells were used to evaluate the chernopreventive effect of T catappa water extract (TCE) and punicalagin. In the cell proliferation assay, TCE and punicalagin suppressed the proliferation of H-ras-transformed NIH3T3 cells with a dose-dependent manner but only partially affected non-transformed NIH3T3 cells proliferation. The differential cytotoxicity of TCE/punicalagin on the H-ras-transformed and non-transformed NIH3T3 cells indicated the selectivity of TCE/punicalagin against H-ras induced transformation. TCE or punicalagin treatment reduced anchorage-independent growth that could be due to a cell cycle arrest at GO/G1 phase. The intracellular superoxide level, known to modulate downstream signaling of Ras protein, was decreased by punicalagin treatments. The levels of phosphorylated JNK-1 and p38 were also decreased with punicallagin treatments. Thus, the chernopreventive effect of punicalagin against H-ras induced transformation could result from inhibition of the intracellular redox status and JNK-1/p38 activation. (c) 2005 Elsevier Ireland Ltd. All rights reserved.