Combination treatment based on metabolic effects of dinaline

Schaider H., Haberkorn U., Petru E. and Berger M.R. (1995) Combination treatment based on metabolic effects of dinaline. Journal of Cancer Research and Clinical Oncology, 121 4: 203-210. doi:10.1007/BF01366963


Author Schaider H.
Haberkorn U.
Petru E.
Berger M.R.
Title Combination treatment based on metabolic effects of dinaline
Journal name Journal of Cancer Research and Clinical Oncology   Check publisher's open access policy
ISSN 0171-5216
Publication date 1995-01-01
Sub-type Article (original research)
DOI 10.1007/BF01366963
Volume 121
Issue 4
Start page 203
End page 210
Total pages 8
Publisher Springer-Verlag
Language eng
Subject 2730 Oncology
1306 Cancer Research
Abstract The human colon carcinoma cell line SW 707 was exposed for up to 72 h to the new antineoplastic agent 4-amino-N-(2′-aminophenyl)benzamide (GOE 1734, dinaline). Thereafter, uptake measurements with fluorodeoxy-[14C]glucose (FdGlc) were performed and cell-cycle fractions as well as adenine nucleotide pools were determined by flow cytometry and HPLC. One day after a 24 h exposure to 20-540 μM dinaline a 2.0-to 2.5-fold enhancement of FdGlc uptake was observed, and the values after 48-h or 72-h incubations showed a 2.5- to 3.5-fold or a 2.0-fold increase respectively. For all periods of exposure a diminished S phase (3%-71% of control) was found initially after incubation, demonstrating the antiproliferative effect of dinaline, with total recovery after 1 day. Adenine nucleotide pools were not diminished concomitantly. The enhanced FdGlc uptake caused by dinaline was the basis for choosing 2-deoxyglucose (dGlc) as the combination partner, which acts as an antimetabolite to enzymes involved in glucose metabolism. Several combinations of dinaline and dGlc were analyzed for their effects on growth inhibition. Almost 50% additional decrease in cell number as compared to monotherapy with dinaline was found after coexposure to 12 mM dGlc and 20 μM dinaline 24 h after incubation. Similar effects were observed 2 days after incubation with the two drugs. After 3 days, the cell numbers reached monotherapy levels. Since the cytostatic effect of dinaline could be enhanced by dGlc although incubation with dGlc alone caused no changes in cell number, the combined effect of both agents is synergistic. These results imply that dinaline might have applications in combination treatment in vivo.
Keyword 2-Deoxyglucose
2-Fluoro-2-deoxy-d-glucose
Combination treatment
Dinaline
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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