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. MF13 also inhibited human colon cancer growth in nude mice by more than 85% (volume, p<0.001). It acted in a dose-dependent manner and induced a complete regression of tumor in 20% of the mice when the initial dose was high (15 mg/kg, i.p.). 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 the MF13 treated (s.c.) mice underwent an irreversible apoptosis. Side effects of MF13 were the transient depression of hemopoiesis and loss of body weight, which vanished within 9-10 days. LD50 of MF13 of a single i.p. injection was 27 mg/kg (94 mg/m2), 11 times higher than the therapeutic dose of a single injection.
Jiang
J D
JD
Division of Medical Oncology, Mount Sinai School of Medicine, New York, NY 10029, USA. wangy01@doc.mssm.edu
Zhang
H
H
Li
J N
JN
Roboz
J
J
Qiao
W B
WB
Holland
J F
JF
Bekesi
G
G
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000188:drug therapy; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D008558:Melphalan / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008956:Models, Chemical; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D018906:Antineoplastic Agents, Alkylating; D009842:Oligopeptides; C108832:MF 13; C053596:metamelfalan; D008558:Melphalan