Asian Ginseng Extract Inhibits In Vitro and In Vivo Growth of Mouse Lewis Lung Carcinoma via Modulation of ERK-p53 and NF-κB Signaling

Asian ginseng (AG) is the most commonly used medicinal herb in Asian countries. It is often prescribed for cancer patients as a complementary remedy. However, whether AG in fact benefits cancer patients remains unknown because some studies reported that AG facilitates tumor growth, which contradicts its usage as a dietary remedy to cancer patients. In addition, most of research works on ginseng for anti-cancer were using single ginsenoside rather than whole root extracts used in clinics. Thus, intensive studies using the type of ginseng as its clinical form are necessary to validate its benefits to cancer patients. In this study, anti-tumor potency and underlying molecular mechanisms of the ethanol extract of AG (EAG) were examined in mice with Lewis lung carcinoma (LLC-1). We showed that EAG significantly suppressed tumor growth in LLC-1-bearing mice with concomitant down-regulation of PCNA proliferative marker, and it exhibited specific cytotoxicity to cancer cells. EAG also induced MAPK and p53 signaling in LLC-1 cells, which suppressed cyclin B-cdc2 complex and in turn induced G2-M arrest and apoptosis. Although EAG coulcl activate NF-kappa B signaling, the proteasome inhibitor of MG-132 could effectively prevent NF-kappa B targeted gene expression induced by EAG and then sensitize LLC-1 cells to induce EAG-mediated apoptosis. Collectively, EAG in a relatively high dose significantly suppressed tumor growth in LLC-1-bearing mice, indicating that AG may benefit lung cancer patients as a dietary supplement. This is the first report demonstrating possible combination of EAG with proteasome inhibitors could be a novel strategy in anti-cancer treatment. J. Cell. Biochem. 111: 899-910, 2010. (C) 2010 Wiley-Liss, Inc.