Induction of apoptosis in Lewis lung carcinoma cells by an intestinal bacterial metabolite produced from orally administered ginseng protopanaxadiol saponins

摘要

The present study demonstrated that oral administration of an intestinal bacterial metabolite (M1) of protopanaxadiol-type saponin significantly inhibited the tumor growth at the implantation site after intrapulmonary implantation of Lewis lung carcinoma (LLC) cells, and suppressed the metastasis to mediastinal lymph nodes. We also investigated the inhibitory mechanism of M1 on the growth of LLC cells. M1 inhibited the proliferation of LLC cells in a concentration-dependent manner, with characteristic morphological changes at the concentration of 30 μM. Treatment of LLC cells with M1 resulted in marked elevation of the caspase-3 activity, peaking at 2 h, and a subsequent time-dependent induction of apoptosis during the period from 3 to 24 h, as evidenced by DNA fragmentation analysis. Since M1-induced growth inhibition of LLC cells was completely abrogated by the pretreatment with a specific inhibitor of caspase-3, Z-DEVD-FMK, M1 functions via the activation of caspase-3 in the process of apoptosis in LLC cells. Thus, the anti-proliferative activity of M1 against LLC cells is primarily due to the induction of apoptosis via promotion of caspase-3 activity, and this induction may lead to the anti-tumor activity in vivo.