Cytotoxicity, cellular accumulation and DNA binding of oxaliplatin isomers
Oxaliplatin ( trans-l-1,2-diaminocyclohexane oxalato Pt(II); 1 R,2 R-dach, l-OHP), its trans-d isomer (1 S,2 S-dach) and cis-dach (1 R,2 S-dach) isomers were compared in in vitro testing against human ovarian carcinoma cell lines A2780, A2780/CP (cisplatin resistant), A2780/ l-OHP (oxaliplatin resis...
Saved in:
Published in | Cancer letters Vol. 97; no. 2; pp. 177 - 184 |
---|---|
Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Shannon
Elsevier Ireland Ltd
06.11.1995
Elsevier |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Oxaliplatin (
trans-l-1,2-diaminocyclohexane oxalato Pt(II); 1
R,2
R-dach,
l-OHP), its
trans-d isomer (1
S,2
S-dach) and
cis-dach (1
R,2
S-dach) isomers were compared in in vitro testing against human ovarian carcinoma cell lines A2780, A2780/CP (cisplatin resistant), A2780/
l-OHP (oxaliplatin resistant), colon carcinoma cell line HT-29, and murine leukemia cell lines L1210, L1210/CP (cisplatin resistant), and L1210/dach (tetraplatin resistant). The relative molar potency of the three complexes in all the cell lines except A2780/
l-OHP and L1210/dach are
trans-l > trans-d > cis-dach; in A2780/
l-OHP they are
trans-l = trans-d > cis-dach; in L1210/dach
trans-l > trans-d = cis-dach. The A2780/
l-OHP selected for
trans-l resistance is 3.6-fold resistant to oxaliplatin, showed no resistance to
trans-d isomer and is 6-fold resistant to
cis-dach. However, L1210/dach which is selected for carboxyphthalato 1,2-dach (
trans-dl) platinum(II) is 140-fold resistant to oxaliplatin, 73-fold resistant to
trans-d, and 41-fold resistant to
cis-OHP. The accumulation and DNA binding of platinum following a 2-h treatment of A2780 cells with each of the isomers (60 μM) is in the order of
trans-l > cis-dach >
trans-d which corresponded to the cytotoxicity of
trans-l, but not the others. The data suggest that other processes, such as differential formation of specific adducts and/or repair may be involved. Of the three isomers
l-OHP is the superior and its accumulation and DNA binding are consistent with its cytotoxicity. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0304-3835 1872-7980 |
DOI: | 10.1016/0304-3835(95)03974-2 |