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J Pharmacol Exp Ther. 2002 Dec;303(3):1273-82.

Nitric oxide-donating nonsteroidal anti-inflammatory drugs inhibit the growth of various cultured human cancer cells: evidence of a tissue type-independent effect.

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  • 1American Health Foundation, Valhalla, New York, USA.

Erratum in

  • J Pharmacol Exp Ther. 2003 Nov;307(2):829. Ryan Yassir [corrected to Rayyan Yassir].
  • J Pharmacol Exp Ther. 2003 Jul;306(1):421. Ryann Yaser [corrected to Ryan Yassir].

Abstract

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 IC(50) 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.

PMID:
12438552
DOI:
10.1124/jpet.102.042754
[PubMed - indexed for MEDLINE]
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