Abstract
Ginsenoside Rp1 (G-Rp1) is a novel ginseng saponin derivative with anti-tumor activity. However, the biochemical and molecular mechanisms of G-Rp1 on anti-tumor activity are not fully understood. In the present study, we report that G-Rp1 inhibits lung cancer cell proliferation, migration and adhesion in p53 wild-type A549 and p53-defi cient H1299 cells. Anti-proliferative activity of G-Rp1 in lung cancer cells is mediated by enhanced nuclear localization of cyclin-dependent kinase inhibitors including <TEX>$p27^{Kip1}$</TEX> and <TEX>$p21^{WAF1/Cip1}$</TEX>, and subsequent inhibition of pRb phosphorylation. We also show that these anti-tumor activities of G-Rp1 in both A549 and H1299 cells appear to be mediated by suppression of mitogenic signaling pathways such as ERK, Akt and <TEX>$p70^{S6K}$</TEX>. Taken together, these findings suggest further development and evaluation of G-Rp1 for the treatment of lung cancers with mutated p53 as well as wild-type p53.
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