Growth inhibition of human osteosarcoma HuO9 cells by methylglyoxal bis(cyclopentylamidinohydrazone) in vitro and in vivo

Polyamines are considered to be important intracellular molecules for the p roliferation of cancer cells. In this study, effects of methyl-glyoxal bis( cyclopentylamidinohydrazone) (MGBCP), a potent inhibitor of the polyamine b iosynthetic pathway, on the growth of human osteosarcoma HuO9 cells have be en investigated. MGBCP dose-dependently inhibited the growth of HuO9 cells, in which the contents of spermine, spermidine and putrescine decreased con comitantly. The MGBCP-treated cells clearly exhibited morphological changes , indicating the blebbing and chromatin condensation which are characterist ic of apoptosis. Characteristic oligonucleosomal-sized DNA fragments were o bserved in the MGBCP-treated cells. In in vivo experiments MGBCP (20 or 50 mg/kg) inhibited the growth of transplanted HuO9 tumors in mice. These find ings suggest that the inhibition of polyamine synthesis results in the supp ression of growth of osteosarcoma HuO9 cells, eventually inducing apoptosis in these human osteosarcoma cells in vitro and in vivo.