Inhibition of in vitro tumor cell invasion by transmethylation inhibitors.

Three inhibitors of S-adenosylmethionine-mediated transmethylation, 5'-methylthioadenosine (MTA), 2'-deoxyadenosine and sinefungin, inhibited in vitro invasion by a highly invasive clone (Cl-30) of rat ascites hepatoma cells, AH 130 (AH cells). Difluoromethylthioadenosine (DFMTA), a non-metabolizable derivative of MTA, also caused strong inhibition of invasion at concentrations that did not suppress the growth of the tumor cells. Cl-30 cells precultured in methionine-depleted medium showed decreased invasiveness. DFMTA was also effective on the invasion by fibrosarcoma, B16 melanoma and human lung carcinoma cell lines.