Cytostatic activity of a 5-fluoro-2'-deoxyuridine-alendronate conjugate against gastric adenocarcinoma and non-malignant intestinal and fibroblast cell lines.
BACKGROUND
5-Fluoro-2'-deoxyuridine (5-FdU), a drug against gastric cancer, was covalently linked via its nucleobase with the amino-bisphosphonate alendronate (Ale), resulting in a new antimetabolite-bisphosphonate conjugate (5-FdU-Ale), designed for bone-targeting.


METHODS
The cytostatic effect of 5-FdU-Ale was evaluated in vitro compared to monomers and mixtures using CASY Technologies and the human gastric adenocarcinoma cell lines 23132/87 and MKN-45, in comparison to the intestinal CCL-241 and dermal fibroblast NHDF neonatal cell lines.


RESULTS
The adenocarcinoma cell lines demonstrated a slightly higher sensitivity, with respect to the cell lines CCL-241 and NHDF, to incubation with 5-FdU-Ale. In comparison to 5-FdU, 5-FU and an equimolar mixture of Ale+5-FdU and Ale+5-FU, the cytostatic activity of the 5-FdU-Ale was markedly reduced.


CONCLUSIONS
5-FdU-Ale was only partially or not at all metabolized to a mixture of cytostatic metabolites in vitro. Therefore an in vivo evaluation of the conjugates is indicated.
Department of General, Visceral and Transplant Surgery, University of Tübingen, Waldhörnlestr 22, 72072 Tübingen, Germany. juergen.weinreich@med.uni-tuebingen.de
Jürgen
J
Weinreich
Timm C
TC
Schott
Ingmar
I
Königsrainer
Markus
M
Küper
Alfred
A
Königsrainer
Herbert
H
Schott
D000230:Adenocarcinoma / Q000556:secondary*; D019386:Alendronate / Q000031:analogs & derivatives* / Q000494:pharmacology; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000556:secondary*; D002460:Cell Line; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005347:Fibroblasts / Q000187:drug effects; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007422:Intestines / Q000187:drug effects; D013274:Stomach Neoplasms / Q000473:pathology*
C575868:5-FdU-alendronate; D050071:Bone Density Conservation Agents; D054697:Cytostatic Agents; D005472:Fluorouracil; D019386:Alendronate