Polyamine synthesis inhibitor, methylglyoxal bis (cyclopentylamidino hydrazone) (MGBCP) induces apoptosis in cultured rheumatoid synoviocytes and rheumatoid synovial tissue grafted into mice

To investigate effects of a polyamine synthesis inhibitor, methyl-glyoxal b is (cyclopentylamidinohydrazone) (MGBCP), on the growth and induction of pr ogrammed cell death (apoptosis) of both cultured rheumatoid synoviocytes in vitro and the rheumatoid synovial tissue grafted into SCID mice in vivo. MGBCP inhibited the growth of RA synoviocytes in a dose-dependent manner by depletion of polyamine contents in the cells. Treatment of RA synoviocytes with MGBCP induced apoptosis in the cultured synoviocytes. Administration of MGBCP at two doses of 20 or 50 mg/kg into the grafted IIA tissue induced apoptosis as demonstrated by morphological change and DNA fragmentation in the tissue. The present data suggest that artificial induction of apoptosis through the injection of MGBCP may remove rheumatoid synovitis. These findings suggest that the inhibition of polyamine synthesis results in the suppression of t he growth of RA synoviocytes by inducing apoptosis in the human rheumatoid synovial tissue in vitro and in vivo.