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- Title
Methotrexate-gelonin conjugate - an inhibitor of MCF-7 cells expressing the dihydrofolate receptor.
- Authors
Badr, Mohamed; Kopp, Christian; Theison, Sandra; Meyer, Jennifer; Trommer, Wolfgang E.
- Abstract
An immunotoxin composed of gelonin, a basic ribosome-inactivating protein, type I of 30 kDa, isolated from the seeds of the Indian plant Gelonium multiflorum and methotrexate (MTX) has been studied as a potential tool of gelonin delivery into the cytoplasm of MTX-responsive cells. On the average, about five molecules of methotrexate were chemically coupled to gelonin via an N-hydroxysuccinimide ester of the drug. The MTX-gelonin conjugate was able to reduce the viability of MCF-7 cells in a dose-dependent manner with ID50 of 10 n m, whereas gelonin or MTX alone showed none or very little effects. Besides its ribosome-inactivating activity, which is about ten-fold lower in an in vitro translation assay (IC50 of 50.5 ng/ml as compared to 4.6 ng/ml), the conjugate also significantly induced direct and oxidative DNA damage as shown by the alkaline comet assay. Hence, MTX-gelonin conjugates are promising candidates for the treatment of MTX-responsive cancers.
- Subjects
ANTIBODY-toxin conjugates; GELONIN; RIBOSOME-inactivating proteins; METHOTREXATE; OXIDATIVE coupling; DNA damage
- Publication
Biological Chemistry, 2014, Vol 395, Issue 12, p1461
- ISSN
1431-6730
- Publication type
Article
- DOI
10.1515/hsz-2013-0270