LOX/COX inhibitors enhance the antineoplastic effects of all-trans retinoic acid in osteosarcoma cell lines
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Cell Differentiation drug effects MeSH
- Celecoxib MeSH
- Cyclooxygenase Inhibitors pharmacology MeSH
- Lipoxygenase Inhibitors pharmacology MeSH
- Caffeic Acids pharmacology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Bone Neoplasms drug therapy pathology MeSH
- Osteosarcoma drug therapy pathology MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents pharmacology MeSH
- Pyrazoles pharmacology MeSH
- Sulfonamides pharmacology MeSH
- Tretinoin pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- caffeic acid MeSH Browser
- Celecoxib MeSH
- Cyclooxygenase Inhibitors MeSH
- Lipoxygenase Inhibitors MeSH
- Caffeic Acids MeSH
- Antineoplastic Agents MeSH
- Pyrazoles MeSH
- Sulfonamides MeSH
- Tretinoin MeSH
The induced differentiation of tumor cells into mature phenotypes is a promising strategy in cancer therapy. In this study, the effects of combined treatment with all-trans retinoic acid (ATRA) and lipoxygenase/cyclooxygenase inhibitors were examined in two osteosarcoma cell lines, Saos-2 and OSA-01. Caffeic acid and celecoxib were used as inhibitors of 5-lipoxygenase and of cyclooxygenase-2, respectively. Changes in the cell proliferation, matrix mineralization, and occurrence of differentiation markers were evaluated in treated cell populations at intervals. The results confirmed the capability of caffeic acid to enhance the antiproliferative effect of ATRA in both cell lines. In contrast, celecoxib showed the same effect in Saos-2 cells only. Furthermore, the extension of matrix mineralization was observed after combined treatment with ATRA and celecoxib or caffeic acid. The increased expression of osteogenic differentiation markers was observed in both cell lines after the combined application of ATRA and inhibitors. The obtained results clearly demonstrate the capability of lipoxygenase/cyclooxygenase inhibitors to enhance the antiproliferative and differentiating effect of ATRA in osteosarcoma cells, although some of these effects are specific and depend on the biological features of the respective tumor or cell line.
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