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.

Laboratory of Tumor Biology Department of Experimental Biology School of Science Masaryk University Kotlarska 2 611 37 Brno Czech Republic

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J Exp Clin Cancer Res. 2010 May 11;29:45 PubMed

Pediatr Blood Cancer. 2013 Jun;60(6):1009-15 PubMed

Int J Mol Sci. 2012;13(5):6236-45 PubMed

Med Hypotheses. 2012 Jul;79(1):98-100 PubMed

J Cell Physiol. 2008 Jul;216(1):144-52 PubMed

Clin Epidemiol. 2013 May 16;5:147-62 PubMed

Biochim Biophys Acta. 2000 Apr 6;1474(2):219-25 PubMed

BMC Cancer. 2008 Oct 16;8:300 PubMed

Am J Vet Res. 2000 Oct;61(10):1241-4 PubMed

Gen Pharmacol. 1999 Jan;32(1):143-54 PubMed

Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3342-7 PubMed

Cell Tissue Res. 2010 May;340(2):323-33 PubMed

Adolesc Med State Art Rev. 2007 May;18(1):62-78, ix PubMed

Int J Cancer. 2005 Jun 20;115(3):484-92 PubMed

Cancer Res. 2000 Feb 1;60(3):672-8 PubMed

Expert Rev Anticancer Ther. 2009 Apr;9(4):511-23 PubMed

Tumour Biol. 2013 Oct;34(5):2489-95 PubMed

Cancer Res. 2005 May 15;65(10):4181-90 PubMed

Mediterr J Hematol Infect Dis. 2011;3(1):e2011059 PubMed

J Cell Biochem. 2011 Apr;112(4):1035-45 PubMed

Front Oncol. 2013 May 31;3:132 PubMed

Molecules. 2011 Jul 27;16(8):6365-77 PubMed

Bone. 1995 Aug;17(2 Suppl):77S-83S PubMed

Exp Mol Med. 2007 Aug 31;39(4):469-76 PubMed

Cancer Immunol Immunother. 2007 May;56(5):615-25 PubMed

Appl Immunohistochem Mol Morphol. 2007 Mar;15(1):70-6 PubMed

Br J Pharmacol. 2000 Oct;131(4):851-7 PubMed

Leuk Res. 1998 Feb;22(2):153-61 PubMed

J Steroid Biochem Mol Biol. 1997 Jan;60(1-2):87-97 PubMed

Clin Cancer Res. 2010 Apr 15;16(8):2235-45 PubMed

Onkologie. 2006 Jul;29(7):308-13 PubMed

Pharmacol Rev. 2006 Sep;58(3):621-81 PubMed

Oncology. 2012;82(5):249-60 PubMed

Front Oncol. 2013 Jun 27;3:168 PubMed

Int J Mol Med. 2004 Aug;14(2):305-10 PubMed

Nat Methods. 2012 Jul;9(7):671-5 PubMed

PLoS One. 2013 Jul 09;8(7):e68859 PubMed

Toxicol In Vitro. 2012 Feb;26(1):142-9 PubMed

Int J Mol Med. 2010 Feb;25(2):271-80 PubMed

Cancer Treat Res. 2009;152:3-13 PubMed

Blood. 1996 Aug 1;88(3):1052-61 PubMed

J Int Med Res. 2010 Jul-Aug;38(4):1294-304 PubMed

Int J Oncol. 2012 Jul;41(1):153-60 PubMed

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