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

The　present　study　demonstrated　that　oral　administration　of　an　intestinal　bacterial　metabolite（M1） of　protopanaxadio1－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　Ml　on　the　growth　of　LLC cells．MI　inhibitedtheproliferationofLLCcellsinaconcentration－dependentmanner，withcharacteris－ tic　morphological　changes　at　the　concentration　of30μM．Treatment　of　LLC　cells　with　MI　resulted　in marked　elevation　of　the　caspase－3activity，peaking　at2h，and　a　subsequent　time－dependent　induction of　apoptosis　during　the　period　from3to24h，as　evidencedby　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，MI　fmctions　via　the　activation　of　caspase－3in　the　process　of apoptosis　in　LLC　cells．Thus，the　anti－proliferative　activity　ofMl　against　LLC　cells　is　primarily　dueto the　induction　of　apoptosis　via　promotion　of　caspase－3activity，and　this　induction　may　lead　to　the　anti－