DIOXOPIPERAZINE DERIVATIVE POTENTIATES ANTITUMOR EFFECT OF METHYLGLYOXAL BIS(CYCLOPENTYLAMIDINOHYDRAZONE) ON HUMAN AND MOUSE LEUKEMIA-CELLS

Antiproliferative effects of -4-isobutoxy-carbonyloxymethyl-3,5-dioxop iperazine (MST-16), an inhibitor of topoisomerase II, in combination w ith methyl-glyoxal bis (cyclopentylamidinohydrazone) (MGBCP), an inhib itor for polyamine biosynthetic enzymes, were invdstigated using cultu red human lymphoid cells and leukemic mice. The combined treatment of human Molt 4B lymphoid cells with MST-16 and MGBCP resulted in greater suppressions of cellular polyamine and protein biosyntheses and decre ase of cell number than in the cells treated with either drug alone. I nhibition of macromolecule biosyntheses by MGBCP was additively potent iated by simultaneous treatment with MST-16. In vivo experiments, the combination of MST-16 and MGBCP markedly prolonged die survival time o f mice bearings P388 or L1210 leukemia. These results suggest that goo d antitumor activity of combined treatment with MST-16 and MGBCP resul ted from the diminution of DNA condensation and cellular proliferation caused by inhibition of topoisomerase II with MST-16 and by polyamine depletion with MGBCP.