Original Articles

Antineoplastic action and toxicity of probimane and its effect on immunologic functions in mice

Authors: Tan-Mu Zhang, Mian-Yin Wang, Qing-Duan Wang, Yun-Feng Ren

Abstract

Probimane(AT-2153, MST-02), dlbis(4-morpholinomethyl-3,5-dioxopiperazin-1-yl) propane, exhibited good antitumor activities against S 37,L 1210, L 615, brain tumor B 22 and hepatoma HCS. The 50% inhibitory doses (ID50) of probimane against S 37 were ip 2.8 (2.3-3.4) and ig 4,0 (3.5-4.6) mg/(kg∙d)×8d. At the dosage of 12.5 mg/kg insufficient to inhibit the primary lesion of Lewis lung cancer in mice, probimane decreased the number of the metastatic lesions in the lungs.
The acute ip LD50 in mice was 376 (361-392) mg/kg, whereas the 8-day subacute LD50 in mice were ip l65 (159—172) mg/kg and ig 112 (107-116) mg/kg. The chemotherapeutic indices (LD50/ID50) of probimane were 59 (ip) and 28 (ig).
Subacute toxicity test in rats showed that probimane at the tolerated doses (60 mg/kg∙d) caused slight decrease in platelet count but no significant changes in WBC count, Hb value and liver and kidney functions. No morphological damages in liver, kidney, stomach, intestine, heart and brain were noted.
At the dosage of 25 mg/kg ip or ig, probimane depressed the humoral-mediated immunity in hemolysin formation test, but did not inhibit the cell-mediated immunity in graft vs host reaction and tumor concomitant immunity tests in mice.
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