The selective cyclooxygenase-1 inhibitor SC-560 suppresses cell proliferation and induces apoptosis in human hepatocellular carcinoma cells

  • Authors:
    • Nadia Lampiasi
    • Daniela Foderà
    • Natale D'Alessandro
    • Antonella Cusimano
    • Antonina Azzolina
    • Claudio Tripodo
    • Ada Maria Florena
    • Marta Ida Minervini
    • Monica Notarbartolo
    • Giuseppe Montalto
    • Melchiorre Cervello
  • View Affiliations

  • Published online on: February 1, 2006     https://doi.org/10.3892/ijmm.17.2.245
  • Pages: 245-252
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Abstract

Two isoforms of cyclooxygenase (COX) are known, and to date most studies have implicated COX-2 in the development and progression of various human cancers. Increasing evidence suggests that COX-1 may also play a similar role. Indeed, we have recently observed that the dual COX-1/COX-2 inhibitor indomethacin induces apoptosis in human hepatocellular carcinoma (HCC) cell lines more effectively than the selective COX-2 inhibitors, possibly implicating COX-1 in HCC. In this study we investigated the expression of COX-1 in non-tumor and malignant human liver tissues, as well as the effects of the highly selective COX-1 inhibitor SC-560 on cell growth and apoptosis in human HCC cell lines. Expression of COX-1 was detected in nearly all the samples assayed, although with a high variability between non-tumoral (NT) and malignant tissues. The percentage of COX-1 positive cells was significantly higher in the NT tissues than in the tumors (p<0.0001). In well-differentiated HCC COX-1 expression was significantly higher than in the poorly-differentiated tissues (p<0.05). SC-560 showed a dose- and time-dependent inhibitory effect on HCC cell growth. The combination of the COX-1 inhibitor with nimesulide and CAY10404, two selective COX-2 inhibitors, resulted in additive effects on cell growth inhibition. SC-560 also inhibited colony formation in soft agar and induced apoptosis in HCC cells in a dose-dependent manner. Moreover, SC-560 decreased the levels of the anti-apoptotic proteins survivin and XIAP and activated caspase-3 and -7 in a dose- and time-dependent fashion. In conclusion, we report for the first time that the selective COX-1 inhibitor SC-560 exhibits anti-tumor and apoptotic effects in human HCC cells. Overall, our previous and present results suggest that both COX-1 and COX-2 inhibitors may have potential therapeutic implications in HCC patients.

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February 2006
Volume 17 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Lampiasi N, Foderà D, D'Alessandro N, Cusimano A, Azzolina A, Tripodo C, Florena AM, Minervini MI, Notarbartolo M, Montalto G, Montalto G, et al: The selective cyclooxygenase-1 inhibitor SC-560 suppresses cell proliferation and induces apoptosis in human hepatocellular carcinoma cells. Int J Mol Med 17: 245-252, 2006
APA
Lampiasi, N., Foderà, D., D'Alessandro, N., Cusimano, A., Azzolina, A., Tripodo, C. ... Cervello, M. (2006). The selective cyclooxygenase-1 inhibitor SC-560 suppresses cell proliferation and induces apoptosis in human hepatocellular carcinoma cells. International Journal of Molecular Medicine, 17, 245-252. https://doi.org/10.3892/ijmm.17.2.245
MLA
Lampiasi, N., Foderà, D., D'Alessandro, N., Cusimano, A., Azzolina, A., Tripodo, C., Florena, A. M., Minervini, M. I., Notarbartolo, M., Montalto, G., Cervello, M."The selective cyclooxygenase-1 inhibitor SC-560 suppresses cell proliferation and induces apoptosis in human hepatocellular carcinoma cells". International Journal of Molecular Medicine 17.2 (2006): 245-252.
Chicago
Lampiasi, N., Foderà, D., D'Alessandro, N., Cusimano, A., Azzolina, A., Tripodo, C., Florena, A. M., Minervini, M. I., Notarbartolo, M., Montalto, G., Cervello, M."The selective cyclooxygenase-1 inhibitor SC-560 suppresses cell proliferation and induces apoptosis in human hepatocellular carcinoma cells". International Journal of Molecular Medicine 17, no. 2 (2006): 245-252. https://doi.org/10.3892/ijmm.17.2.245