Selective growth inhibition of cancer cells by L-methioninase-containing fusion protein targeted to the urokinase receptor.
BACKGROUND
We have reported the development of a novel fusion protein (FP) consisting of an amino-terminal fragment of urokinase linked to the amino terminus of the enzyme L-methioninase (L-M). The present study compared the effect of this novel FP on the proliferation of human ovarian, skin, breast endometrial and pancreatic cancer cell lines.


METHODS
The FP, L-M and a mutated FP, with reduced L-M activity, were produced by recombinant methods. The effect of treatment with FP, L-M and mutated FP on the proliferation of the cancer cells was measured in vitro using an MTS assay.


RESULTS
The inhibitory effect of the FP was found to be significantly greater than that of L-M alone or the mutated FP. In addition, the FP produced a greater inhibitory effect on an ovarian cancer cell line than on comparable normal, non-cancerous cells. Further, the FP produced a dose-dependent inhibition of the proliferation of pancreatic cancer cell lines.


CONCLUSIONS
These results suggest that this FP is a potent and selective inhibitor of the proliferation of various cancer cell lines and has potential as a therapeutic agent for the treatment of various methionine-dependent cancers.
Bioengineering Center and School of Chemical, Biological and Materials Engineering, University of Oklahoma, Norman, Oklahoma 73117, USA.
Naveen R
NR
Palwai
Xiao-Ping
XP
Zang
Roger G
RG
Harrison
Doris
D
Benbrook
J Thomas
JT
Pento
D000970:Antineoplastic Agents / Q000494:pharmacology*; D013437:Carbon-Sulfur Lyases / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006801:Humans; D009154:Mutation; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*
D000970:Antineoplastic Agents; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins; D013437:Carbon-Sulfur Lyases; C021558:L-methionine gamma-lyase