![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 303, Issue 3, 1273-1282, December 2002
American Health Foundation, Valhalla, New York (K.K., J.L.W., J.C.,
B.R.); Department of Physiology and Pharmacology, City University of
New York Medical School, New York, New York (K.K.); Sarah C. Upham
Division of Gastroenterology, New York Medical College, Valhalla, New
York (Y.R., J.L.W., P.d.S., B.R.); University of Iowa Hospitals and
Clinics, Iowa City, Iowa (L.L.Q.); and Brader Cancer Research
Institute, Department of Medicine, New York Medical College, Valhalla,
New York (F.T.)
The novel nitric oxide (NO)-donating nonsteroidal anti-inflammatory
drugs (NO-NSAIDs), which are safer than their NSAID counterparts, inhibit the growth of colon cancer cells with far greater potency than
traditional NSAIDs. We examined whether NO-NSAIDs inhibit the growth of
cancer cells arising from other human tissues. Human pancreatic, colon,
prostate, lung, and tongue cancer cell lines were treated with
NO-aspirin, -sulindac, -ibuprofen, and -indomethacin or their
traditional counterparts. We determined IC50 values, cell
proliferation, apoptosis, cell cycle, cyclooxygenase (COX) protein
levels, and morphological changes (light and electron microscopy). All
NO-NSAIDs inhibited the growth of all cancer cell lines studied. The
potency of NO-NSAIDs was 11- to 6000-fold greater than that of their
counterparts (except for the effect of sulindac on lung cancer cells).
NO-aspirin was consistently the most potent NO-NSAID in all cell lines
tested (except for the lung cancer cell line), sometimes in excess of
100-fold over the other three NO-NSAIDs. NO-NSAIDs inhibited cell
proliferation, induced apoptosis, and altered cell cycle phase
distribution (G2/M to G0/G1 block).
All altered cellular morphology, whereas NO-aspirin induced nuclear
disintegration ("atypical" cells) established by electron
microscopy. NO-aspirin showed similar effects on two pancreatic cancer
cell lines, BxPC-3 (expresses COX) and MIA PaCa-2 (no COX expression),
suggesting a COX-independent effect. NO-NSAIDs showed a
tissue-type-independent effect. Their pleiotropic effects involve cell
renewal, cell death, and cell cycle phase transitions. These results
raise the possibility that NO-NSAIDs possess chemopreventive and/or
chemotherapeutic activity against a wide variety of human cancers.
This article has been cited by other articles:
|
|
 |
|
  N. Katayama, K. Nakajou, H. Komori, K. Uchida, J.-i. Yokoe, N. Yasui, H. Yamamoto, T. Kai, M. Sato, T. Nakagawa, et al. Design and Evaluation of S-Nitrosylated Human Serum Albumin as a Novel Anticancer Drug J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 69 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Maksimovic-Ivanic, S. Mijatovic, L. Harhaji, D. Miljkovic, D. Dabideen, K. Fan Cheng, K. Mangano, G. Malaponte, Y. Al-Abed, M. Libra, et al. Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo Mol. Cancer Ther., March 1, 2008; 7(3): 510 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Williams, P. Ji, N. Ouyang, X. Liu, and B. Rigas NO-donating aspirin inhibits the activation of NF-{kappa}B in human cancer cell lines and Min mice Carcinogenesis, February 1, 2008; 29(2): 390 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. McIlhatton, J. Tyler, S. Burkholder, J. Ruschoff, B. Rigas, L. Kopelovich, and R. Fishel Nitric Oxide Donating Aspirin Derivatives Suppress Microsatellite Instability in Mismatch Repair Deficient and Hereditary Nonpolyposis Colorectal Cancer Cells Cancer Res., November 15, 2007; 67(22): 10966 - 10975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Hagos, R. E. Carroll, T. Kouznetsova, Q. Li, V. Toader, P. A. Fernandez, S. M. Swanson, and G. R.J. Thatcher Colon cancer chemoprevention by a novel NO chimera that shows anti-inflammatory and antiproliferative activity in vitro and in vivo Mol. Cancer Ther., August 1, 2007; 6(8): 2230 - 2239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. F. Zerbini, A. Czibere, Y. Wang, R. G. Correa, H. Otu, M. Joseph, Y. Takayasu, M. Silver, X. Gu, K. Ruchusatsawat, et al. A Novel Pathway Involving Melanoma Differentiation Associated Gene-7/Interleukin-24 Mediates Nonsteroidal Anti-inflammatory Drug-Induced Apoptosis and Growth Arrest of Cancer Cells Cancer Res., December 15, 2006; 66(24): 11922 - 11931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Rao, B. S. Reddy, V. E. Steele, C-X Wang, X. Liu, N. Ouyang, J. M.R. Patlolla, B. Simi, L. Kopelovich, and B. Rigas Nitric oxide-releasing aspirin and indomethacin are potent inhibitors against colon cancer in azoxymethane-treated rats: effects on molecular targets. Mol. Cancer Ther., June 1, 2006; 5(6): 1530 - 1538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ouyang, J. L. Williams, G. J. Tsioulias, J. Gao, M. J. Iatropoulos, L. Kopelovich, K. Kashfi, and B. Rigas Nitric oxide-donating aspirin prevents pancreatic cancer in a hamster tumor model. Cancer Res., April 15, 2006; 66(8): 4503 - 4511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Gao, K. Kashfi, X. Liu, and B. Rigas NO-donating aspirin induces phase II enzymes in vitro and in vivo Carcinogenesis, April 1, 2006; 27(4): 803 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bratasz, N. M. Weir, N. L. Parinandi, J. L. Zweier, R. Sridhar, L. J. Ignarro, and P. Kuppusamy Reversal to cisplatin sensitivity in recurrent human ovarian cancer cells by NCX-4016, a nitro derivative of aspirin PNAS, March 7, 2006; 103(10): 3914 - 3919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ouyang, J. L. Williams, and B. Rigas NO-donating aspirin isomers downregulate peroxisome proliferator-activated receptor (PPAR){delta} expression in APCmin/+ mice proportionally to their tumor inhibitory effect: Implications for the role of PPAR{delta} in carcinogenesis Carcinogenesis, February 1, 2006; 27(2): 232 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Hundley and B. Rigas Nitric Oxide-Donating Aspirin Inhibits Colon Cancer Cell Growth via Mitogen-Activated Protein Kinase Activation J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 25 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Gao, X. Liu, and B. Rigas Nitric oxide-donating aspirin induces apoptosis in human colon cancer cells through induction of oxidative stress PNAS, November 22, 2005; 102(47): 17207 - 17212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Goel, C. Gasche, and C. R. Boland Chemoprevention Goes Gourmet: Different Flavors of NO-Aspirin Mol. Interv., August 1, 2005; 5(4): 207 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Gao, K. Kashfi, and B. Rigas In Vitro Metabolism of Nitric Oxide-Donating Aspirin: The Effect of Positional Isomerism J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 989 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kashfi, S. Borgo, J. L. Williams, J. Chen, J. Gao, A. Glekas, F. Benedini, P. del Soldato, and B. Rigas Positional Isomerism Markedly Affects the Growth Inhibition of Colon Cancer Cells by Nitric Oxide-Donating Aspirin in Vitro and in Vivo J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 978 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Huguenin, F. Vacherot, L. Kheuang, J. Fleury-Feith, M.-C. Jaurand, M. Bolla, J.-P. Riffaud, and D. K. Chopin Antiproliferative effect of nitrosulindac (NCX 1102), a new nitric oxide-donating non-steroidal anti-inflammatory drug, on human bladder carcinoma cell lines Mol. Cancer Ther., March 1, 2004; 3(3): 291 - 298. [Abstract] [Full Text]
|
|
|
|
|
|
J. L. Williams, N. Nath, J. Chen, T. R. Hundley, J. Gao, L. Kopelovich, K. Kashfi, and B. Rigas Growth Inhibition of Human Colon Cancer Cells by Nitric Oxide (NO)-Donating Aspirin Is Associated with Cyclooxygenase-2 Induction and {beta}-Catenin/T-Cell Factor Signaling, Nuclear Factor-{kappa}B, and NO Synthase 2 Inhibition: Implications for Chemoprevention Cancer Res., November 15, 2003; 63(22): 7613 - 7618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nath, K. Kashfi, J. Chen, and B. Rigas Nitric oxide-donating aspirin inhibits {beta}-catenin/T cell factor (TCF) signaling in SW480 colon cancer cells by disrupting the nuclear {beta}-catenin-TCF association PNAS, October 28, 2003; 100(22): 12584 - 12589. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
