High anticancer efficacy of L-proline-m-bis (2-chloroethyl) amino-L-phenylalanyl-L-norvaline ethyl ester hydrochloride (MF13) in vivo

The anticancer efficacy of the new anticancer tripeptide, L-proline-m-bis ( 2-chloroethyl) amino-L phenylalanyl-L-norvaline ethyl ester hydrochloride ( MF13), was investigated in mice. MF13 showed a therapeutic effect in liquid tumors and induced complete remission even in late stage malignancies. MF1 3 also inhibited human colon cancer growth in nude mice by more than 85% (v olume, p < 0.001). It acted in a dose-dependent manner and induced a comple te regression of tumor in 20 % of the mice when the initial dose was high ( 15 mg/kg, ip). Human melanoma exhibited a response to MF13 similar to colon cancer: Activity of MF13 in murine hepatoma in vivo was stronger than its precursor m-sarcolysin (p < 0.001). Tumor cells in peritoneal cavities of t he MF13 treated (sc) mice underwent an irreversible apoptosis. Side effects of MF13 were the transient depression of hemopoiesis and loss of body weig ht, which vanished within 9-10 days. LD50 of MF13 of a single ip injection was 27 mg/kg (94 mg/m(2)), 11 times higher than the therapeutic dose of a s ingle injection.