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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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Article

DNA-hypomethylating agent, 5'-azacytidine, induces cyclooxygenase-2 expression via the PI3-kinase/Akt and extracellular signal-regulated kinase-1/2 pathways in human HT1080 fibrosarcoma cells

  • Authors:
    • Seon-Mi Yu
    • Song-Ja Kim
  • View Affiliations / Copyright

    Affiliations: Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju 182, Republic of Korea
  • Pages: 1469-1475
    |
    Published online on: July 31, 2015
       https://doi.org/10.3892/ijo.2015.3110
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Abstract

The cytosine analogue 5'-azacytidine (5'-aza) induces DNA hypomethylation by inhibiting DNA methyltransferase. In clinical trials, 5'-aza is widely used in epigenetic anticancer treatments. Accumulated evidence shows that cyclooxygenase-2 (COX-2) is overexpressed in various cancers, indicating that it may play a critical role in carcinogenesis. However, few studies have been performed to explore the molecular mechanism underlying the increased COX-2 expression. Therefore, we tested the hypothesis that 5'-aza regulates COX-2 expression and prostaglandin E2 (PGE2) production. The human fibrosarcoma cell line HT1080, was treated with various concentrations of 5'-aza for different time periods. Protein expressions of COX-2, DNA (cytosine-5)-methyltransferase 1 (DNMT1), pAkt, Akt, extracellular signal-regulated kinase (ERK), and phosphorylated ERK (pERK) were determined using western blot analysis, and COX-2 mRNA expression was determined using RT-PCR. PGE2 production was evaluated using the PGE2 assay kit. The localization and expression of COX-2 were determined using immunofluorescence staining. Treatment with 5'-aza induces protein and mRNA expression of COX-2. We also observed that 5'-aza-induced COX-2 expression and PGE2 production were inhibited by S-adenosylmethionine (SAM), a methyl donor. Treatment with 5'-aza phosphorylates PI3-kinase/Akt and ERK-1/2; inhibition of these pathways by LY294002, an inhibitor of PI3-kinase/Akt, or PD98059, an inhibitor of ERK-1/2, respectively, prevents 5'-aza-induced COX-2 expression and PGE2 production. Overall, these observations indicate that the hypomethylating agent 5'-aza modulates COX-2 expression via the PI3-kinase/Akt and ERK-1/2 pathways in human HT1080 fibrosarcoma cells.
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Copy and paste a formatted citation
Spandidos Publications style
Yu S and Kim S: DNA-hypomethylating agent, 5'-azacytidine, induces cyclooxygenase-2 expression via the PI3-kinase/Akt and extracellular signal-regulated kinase-1/2 pathways in human HT1080 fibrosarcoma cells . Int J Oncol 47: 1469-1475, 2015.
APA
Yu, S., & Kim, S. (2015). DNA-hypomethylating agent, 5'-azacytidine, induces cyclooxygenase-2 expression via the PI3-kinase/Akt and extracellular signal-regulated kinase-1/2 pathways in human HT1080 fibrosarcoma cells . International Journal of Oncology, 47, 1469-1475. https://doi.org/10.3892/ijo.2015.3110
MLA
Yu, S., Kim, S."DNA-hypomethylating agent, 5'-azacytidine, induces cyclooxygenase-2 expression via the PI3-kinase/Akt and extracellular signal-regulated kinase-1/2 pathways in human HT1080 fibrosarcoma cells ". International Journal of Oncology 47.4 (2015): 1469-1475.
Chicago
Yu, S., Kim, S."DNA-hypomethylating agent, 5'-azacytidine, induces cyclooxygenase-2 expression via the PI3-kinase/Akt and extracellular signal-regulated kinase-1/2 pathways in human HT1080 fibrosarcoma cells ". International Journal of Oncology 47, no. 4 (2015): 1469-1475. https://doi.org/10.3892/ijo.2015.3110
Copy and paste a formatted citation
x
Spandidos Publications style
Yu S and Kim S: DNA-hypomethylating agent, 5'-azacytidine, induces cyclooxygenase-2 expression via the PI3-kinase/Akt and extracellular signal-regulated kinase-1/2 pathways in human HT1080 fibrosarcoma cells . Int J Oncol 47: 1469-1475, 2015.
APA
Yu, S., & Kim, S. (2015). DNA-hypomethylating agent, 5'-azacytidine, induces cyclooxygenase-2 expression via the PI3-kinase/Akt and extracellular signal-regulated kinase-1/2 pathways in human HT1080 fibrosarcoma cells . International Journal of Oncology, 47, 1469-1475. https://doi.org/10.3892/ijo.2015.3110
MLA
Yu, S., Kim, S."DNA-hypomethylating agent, 5'-azacytidine, induces cyclooxygenase-2 expression via the PI3-kinase/Akt and extracellular signal-regulated kinase-1/2 pathways in human HT1080 fibrosarcoma cells ". International Journal of Oncology 47.4 (2015): 1469-1475.
Chicago
Yu, S., Kim, S."DNA-hypomethylating agent, 5'-azacytidine, induces cyclooxygenase-2 expression via the PI3-kinase/Akt and extracellular signal-regulated kinase-1/2 pathways in human HT1080 fibrosarcoma cells ". International Journal of Oncology 47, no. 4 (2015): 1469-1475. https://doi.org/10.3892/ijo.2015.3110
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