An investigation of the cytotoxicity of the morpholino anthracycline MX2 against glioma cells in vitro.
MX2 is a novel morpholino anthracycline reported to have lower systemic toxicity than other anthracyclines. It has similar antitumour activity to adriamycin and is cytotoxic towards multi-drug resistant cells and anthracycline sensitive sublines of human and murine tumour cells. In this study MX2 showed a marked cytocidal effect compared to M2, the most cytotoxically active metabolite, and the nitrosourea, BCNU, when 30 ng/ml of each drug was added to separate flasks of C6 glioma cells grown in monolayer. The colony formation of C6 glioma cells was markedly inhibited by MX2 in a dose dependent manner. The LD50 values for MX2, M2 and BCNU were 10.5 ng/ml, 15.8 ng/ml and 465 ng/ml respectively. MX2 is likely to be bound to the main plasma protein, albumin, and can also interact with the plasma lipoproteins, particularly high density lipoprotein. The results in this study strongly support the further investigation of MX2 as a potential chemotherapeutic agent against brain tumours.
Park
S J
SJ
Department of Surgery, University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia.
Kaye
A H
AH
Hill
J S
JS
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002330:Carmustine / Q000494:pharmacology / Q000627:therapeutic use; D002360:Carubicin / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D008074:Lipoproteins; C053537:morpholinoanthracycline MX2; D002360:Carubicin; D002330:Carmustine