PC-SPES down-regulates COX-2 via inhibition of NF-κB and C/EBPβ in non-small cell lung cancer cells

  • Authors:
    • Takayuki Ikezoe
    • Yang Yang
    • Takayuki Saitoh
    • David Heber
    • Robert McKenna
    • Hirokuni Taguchi
    • H. Phillip Koeffler
  • View Affiliations

  • Published online on: August 1, 2006     https://doi.org/10.3892/ijo.29.2.453
  • Pages: 453-461
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Abstract

Aberrant expression of COX-2 occurs in many types of malignancies including colon and lung cancers, and is implicated in development and progression of cancer. The molecular mechanisms associated with aberrant expression of COX-2 in lung cancer cells remain to be fully elucidated. In this study, we found that non-small cell lung cancer (NSCLC) NCI-H520 and NCI-H460 cells constitutively expressed COX-2 and produced prostaglandin E2 (PGE2) as measured by Western blotting and enzyme-linked immunosorbent assay (ELISA), respectively. Reporter assays showed that transcriptional regulation of COX-2 was blunted when either the NF-IL6 (C/EBPβ) or nuclear factor-κB (NF-κB) binding site in the COX-2 promoter was mutated, suggesting that C/EBPβ and NF-κB transcription factors have an important role in aberrant expression of COX-2 in these lung cancer cells. In addition, the eight herbal mixture PC-SPES (Lot. 5431219) caused growth arrest and apoptosis of NCI-H520 and NCI-H460 cells in association with blockade of NF-κB and down-regulation of C/EBPβ, resulting in down-regulation of COX-2 and PGE2 in these cells. On the other hand, PC-SPES up-regulated the level of C/EBPβ in these cells. Taken together, C/EBPβ and NF-κB may be promising molecular targets for COX-2 inhibition in lung cancer cells. PC-SPES might be useful in the adjuvant setting for the treatment of individuals with resected NSCLC as well as other types of cancer in which COX-2 is activated.

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August 2006
Volume 29 Issue 2

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

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Spandidos Publications style
Ikezoe T, Yang Y, Saitoh T, Heber D, McKenna R, Taguchi H and Koeffler HP: PC-SPES down-regulates COX-2 via inhibition of NF-κB and C/EBPβ in non-small cell lung cancer cells. Int J Oncol 29: 453-461, 2006
APA
Ikezoe, T., Yang, Y., Saitoh, T., Heber, D., McKenna, R., Taguchi, H., & Koeffler, H.P. (2006). PC-SPES down-regulates COX-2 via inhibition of NF-κB and C/EBPβ in non-small cell lung cancer cells. International Journal of Oncology, 29, 453-461. https://doi.org/10.3892/ijo.29.2.453
MLA
Ikezoe, T., Yang, Y., Saitoh, T., Heber, D., McKenna, R., Taguchi, H., Koeffler, H. P."PC-SPES down-regulates COX-2 via inhibition of NF-κB and C/EBPβ in non-small cell lung cancer cells". International Journal of Oncology 29.2 (2006): 453-461.
Chicago
Ikezoe, T., Yang, Y., Saitoh, T., Heber, D., McKenna, R., Taguchi, H., Koeffler, H. P."PC-SPES down-regulates COX-2 via inhibition of NF-κB and C/EBPβ in non-small cell lung cancer cells". International Journal of Oncology 29, no. 2 (2006): 453-461. https://doi.org/10.3892/ijo.29.2.453