NCX 4016, a nitric oxide-releasing aspirin derivative, exhibits a significant antiproliferative effect and alters cell cycle progression in human colon adenocarcinoma cell lines

  • Authors:
    • Anna Tesei
    • Luca Ricotti
    • Paola Ulivi
    • Laura Medri
    • Dino Amadori
    • Wainer Zoli
  • View Affiliations

  • Published online on: June 1, 2003     https://doi.org/10.3892/ijo.22.6.1297
  • Pages: 1297-1302
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Abstract

Nitric oxide-releasing non-steroidal antiinflammatory drugs (NO-NSAIDs) are safer than NSAIDs due to their ability to reduce gastric toxicity. We assessed the cytotoxic activity of a new aspirin derivative, NCX 4016, after different exposure schedules, in three human colon adenocarcinoma cell lines. All the lines were positive for COX-1 protein and mRNA, as evaluated by Western blot and RT-PCR, respectively, while only one was positive for COX-2. The cytostatic and cytocidal activity was determined by sulforhodamine B assay and evaluated according to Monks' model. Cytostatic activity was observed after a 24-h drug exposure and 50% growth inhibition was reached at concentrations ranging from 165 to 250 µM in all cell lines, whereas with aspirin the IC50 was never reached, even at the maximum concentration tested (500 µM), and was independent of COX-1 or COX-2 status. Cytocidal activity was observed only at the highest concentrations and persisted for a long time after drug removal. Flow cytometric analysis showed that the NO-aspirin compound induced a persistent accumulation of cells in G2-M phase in all the cell lines after at least 48 h exposure. Specifically, the block pertained mainly to G2 phase, whereas mitotic index was not affected at all. Our results indicate that NCX 4016 has an in vitro cytostatic activity superior to that of its parental aspirin compound, which makes it a potentially important tumor preventive agent. Furthermore, the cytocidal effect observed at the highest concentrations and the induction of a specific block in G2 phase renders it a promising candidate for drug combination treatments.

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June 2003
Volume 22 Issue 6

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

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Spandidos Publications style
Tesei A, Ricotti L, Ulivi P, Medri L, Amadori D and Zoli W: NCX 4016, a nitric oxide-releasing aspirin derivative, exhibits a significant antiproliferative effect and alters cell cycle progression in human colon adenocarcinoma cell lines. Int J Oncol 22: 1297-1302, 2003
APA
Tesei, A., Ricotti, L., Ulivi, P., Medri, L., Amadori, D., & Zoli, W. (2003). NCX 4016, a nitric oxide-releasing aspirin derivative, exhibits a significant antiproliferative effect and alters cell cycle progression in human colon adenocarcinoma cell lines. International Journal of Oncology, 22, 1297-1302. https://doi.org/10.3892/ijo.22.6.1297
MLA
Tesei, A., Ricotti, L., Ulivi, P., Medri, L., Amadori, D., Zoli, W."NCX 4016, a nitric oxide-releasing aspirin derivative, exhibits a significant antiproliferative effect and alters cell cycle progression in human colon adenocarcinoma cell lines". International Journal of Oncology 22.6 (2003): 1297-1302.
Chicago
Tesei, A., Ricotti, L., Ulivi, P., Medri, L., Amadori, D., Zoli, W."NCX 4016, a nitric oxide-releasing aspirin derivative, exhibits a significant antiproliferative effect and alters cell cycle progression in human colon adenocarcinoma cell lines". International Journal of Oncology 22, no. 6 (2003): 1297-1302. https://doi.org/10.3892/ijo.22.6.1297