RT Journal Article
SR Electronic
T1 Cytostatic Activity of a 5-Fluoro-2’-deoxyuridine–Alendronate Conjugate against Gastric Adenocarcinoma and Non-malignant Intestinal and Fibroblast Cell Lines
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4299
OP 4305
VO 32
IS 10
A1 JÜRGEN WEINREICH
A1 TIMM C. SCHOTT
A1 INGMAR KÖNIGSRAINER
A1 MARKUS KÜPER
A1 ALFRED KÖNIGSRAINER
A1 HERBERT SCHOTT
YR 2012
UL http://ar.iiarjournals.org/content/32/10/4299.abstract
AB 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. Materials and 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. Conclusion: 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.