Abstract |
Nitric oxide-releasing aspirin ( NO-ASA) is emerging as a potentially important chemopreventive agent against colon cancer. We examined in HT-29 human colon adenocarcinoma cells the effect of NO-ASA on the inducible form of nitric oxide synthase (NOS2), an enzyme implicated in colon carcinogenesis. NO-ASA inhibited in a time- and concentration-dependent manner the expression of NOS2 up to 70% compared to control (IC50 for this effect = 46 microM). NO-ASA also decreased the corresponding steady-state mRNA levels and this reduction preceded the reduction of protein levels by at least 6 h. NO-ASA also reduced the enzymatic activity of NOS2, as determined by a direct enzyme assay (maximal reduction = 80%) and by determining the accumulation of NO in the culture medium (IC50 for this effect = 36 microM). These effects of NO-ASA on NOS2 were paralleled by inhibition in cell growth (IC50 = 8.5 microM). These findings indicate that NO-ASA profoundly inhibits both the expression and enzymatic activity of NOS2 and suggest that these effects may represent an important mechanism for the colon cancer chemopreventive effect of NO-ASA.
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Authors | Adam Spiegel, Thomas R Hundley, Jie Chen, Jianjun Gao, Nengtai Ouyang, Xiaoping Liu, Mae F Go, George J Tsioulias, Khosrow Kashfi, Basil Rigas |
Journal | Biochemical pharmacology
(Biochem Pharmacol)
Vol. 70
Issue 7
Pg. 993-1000
(Oct 01 2005)
ISSN: 0006-2952 [Print] England |
PMID | 16105666
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- DNA Primers
- Nitric Oxide Donors
- RNA, Messenger
- NOS2 protein, human
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type II
- Aspirin
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Topics |
- Adenocarcinoma
(enzymology, pathology)
- Aspirin
(pharmacology)
- Base Sequence
- Catalysis
- Colonic Neoplasms
(enzymology, pathology)
- DNA Primers
- HT29 Cells
- Humans
- Nitric Oxide Donors
(pharmacology)
- Nitric Oxide Synthase
(antagonists & inhibitors, genetics, metabolism)
- Nitric Oxide Synthase Type II
- RNA, Messenger
(genetics)
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