COX-2 (cyclo-oxygenase-2) and PGE2 (prostaglandin E2) play a key role in sustaining CRC (colorectal cancer) cell growth and survival. Indeed, the use of agents targeting the COX-2/PGE2 axis has been associated with a reduction in the development of CRC in both humans and murine models of colon carcinogenesis. In the present study, we investigated whether 2-methoxy-5-amino-N-hydroxybenzamide (herein termed 2-14), a derivative of mesalamine that inhibits CRC cell growth both in vitro and in vivo, negatively regulates COX-2/PGE2 expression in CRC cells and assessed whether the 2-14-mediated anti-neoplastic effect is strictly dependent on the inhibition of this pathway. Our results show that 2-14 blocks the growth and enhances the death of HT-115, a CRC cell line overexpressing COX-2, and that these effects associate with inhibition of COX-2 but not COX-1. 2-14 also down-regulates TNFα (tumour necrosis factor α)-induced COX-2 in HT-29 cells as well as COX-2/PGE2 expression in ex vivo cultures of human CRC explants. Similarly, 2-14 reduces COX-2, but not COX-1, in tumoural areas developing in a mouse model of CAC (colitis-associated colon cancer). Finally, we show that 2-14 exhibits in vitro and in vivo anti-mitogenic effects in DLD-1, a COX-deficient CRC cell line. Taken together, these results suggest that 2-14 inhibits CRC cell growth through COX-2-dependent and -independent mechanisms.
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Research Article|
May 16 2012
2-Methoxy-5-amino-N-hydroxybenzamide, a derivative of mesalamine, inhibits colon cancer cell growth through cyclo-oxygenase-2-dependent and -independent mechanisms
Carmine Stolfi;
*Department of Internal Medicine, University of Rome ‘Tor Vergata’, Rome, Italy
Correspondence: Dr Carmine Stolfi (email Carmine.stolfi@uniroma2.it) or Dr Giovanni Monteleone (email Gi.Monteleone@Med.uniroma2.it).
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Eleonora Franzè;
Eleonora Franzè
*Department of Internal Medicine, University of Rome ‘Tor Vergata’, Rome, Italy
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Ivan Monteleone;
Ivan Monteleone
*Department of Internal Medicine, University of Rome ‘Tor Vergata’, Rome, Italy
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Roberta Caruso;
Roberta Caruso
*Department of Internal Medicine, University of Rome ‘Tor Vergata’, Rome, Italy
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Luana Franceschilli;
Luana Franceschilli
†Department of Surgery, University of Rome ‘Tor Vergata’, Rome, Italy
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Pierpaolo Sileri;
Pierpaolo Sileri
†Department of Surgery, University of Rome ‘Tor Vergata’, Rome, Italy
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Giuseppe S. Sica;
Giuseppe S. Sica
†Department of Surgery, University of Rome ‘Tor Vergata’, Rome, Italy
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Achille L. Gaspari;
Achille L. Gaspari
†Department of Surgery, University of Rome ‘Tor Vergata’, Rome, Italy
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Giovanna Del Vecchio Blanco;
Giovanna Del Vecchio Blanco
*Department of Internal Medicine, University of Rome ‘Tor Vergata’, Rome, Italy
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Francesco Pallone;
Francesco Pallone
*Department of Internal Medicine, University of Rome ‘Tor Vergata’, Rome, Italy
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Giovanni Monteleone
*Department of Internal Medicine, University of Rome ‘Tor Vergata’, Rome, Italy
Correspondence: Dr Carmine Stolfi (email Carmine.stolfi@uniroma2.it) or Dr Giovanni Monteleone (email Gi.Monteleone@Med.uniroma2.it).
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Publisher: Portland Press Ltd
Received:
October 28 2011
Revision Received:
February 28 2012
Accepted:
March 21 2012
Accepted Manuscript online:
March 21 2012
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2012 Biochemical Society
2012
Clin Sci (Lond) (2012) 123 (5): 295–306.
Article history
Received:
October 28 2011
Revision Received:
February 28 2012
Accepted:
March 21 2012
Accepted Manuscript online:
March 21 2012
Citation
Carmine Stolfi, Eleonora Franzè, Ivan Monteleone, Roberta Caruso, Luana Franceschilli, Pierpaolo Sileri, Giuseppe S. Sica, Achille L. Gaspari, Giovanna Del Vecchio Blanco, Francesco Pallone, Giovanni Monteleone; 2-Methoxy-5-amino-N-hydroxybenzamide, a derivative of mesalamine, inhibits colon cancer cell growth through cyclo-oxygenase-2-dependent and -independent mechanisms. Clin Sci (Lond) 1 September 2012; 123 (5): 295–306. doi: https://doi.org/10.1042/CS20110556
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