Antitumor Activity and Other Biological Actions of Oligomers of Ribonuclease A
Dimers, trimers, and tetramers of bovine ribonuclease A, obtained by lyophilization of the enzyme from 40% acetic acid solutions, were purified and isolated by cation exchange chromatography. The two conformers constituting each aggregated species were assayed for their antitumor, aspermatogenic, or...
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Published in | The Journal of biological chemistry Vol. 278; no. 26; pp. 23817 - 23822 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
27.06.2003
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Subjects | |
Online Access | Get full text |
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Summary: | Dimers, trimers, and tetramers of bovine ribonuclease A, obtained by lyophilization of the enzyme from 40% acetic acid solutions,
were purified and isolated by cation exchange chromatography. The two conformers constituting each aggregated species were
assayed for their antitumor, aspermatogenic, or embryotoxic activities in comparison with monomeric RNase A and bovine seminal
RNase, which is dimeric in nature. The antitumor action was tested in vitro on ML-2 (human myeloid leukemia) and HL-60 (human myeloid cell line) cells and in vivo on the growth of human non-pigmented melanoma (line UB900518) transplanted subcutaneously in nude mice. RNase A oligomers
display a definite antitumor activity that increases as a function of the size of the oligomers. On ML-2 and HL-60 cells,
dimers and trimers generally show a lower activity than bovine seminal RNase; the activity of tetramers, instead, is similar
to or higher than that of the seminal enzyme. The growth of human melanoma in nude mice is inhibited by RNase A oligomers
in the order dimers < trimers < tetramers. The action of the two tetramers is very strong, blocking almost completely the
growth of melanoma. RNase A dimers, trimers, and tetramers display aspermatogenic effects similar to those of bovine seminal
RNase, but, contrarily, they do not show any embryotoxic activity. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M302711200 |