Ravinder Kodela - NO-releasing NSAIDs suppress NF-κB signaling in vitro and in vivo through S-nitrosylation.

Document created by Ravinder Kodela on Aug 22, 2014
Version 1Show Document
  • View in full screen mode

  Publication Details (including relevant citation   information):

  Cancer Lett. 2010 Dec   8;298(2):204-11. Epub 2010 Jul 31.

  Abstract:

  NO-NSAIDs are promising anticancer drugs, comprising an NSAID, an   NO-releasing moiety, and a spacer linking them. Although the   effect of NO-NSAIDs on a wide variety of signaling and other   cellular mechanisms has been deciphered, a key question remains   unanswered, that being the role of NO to the overall biological   effect of these agents. It has been shown that NO can directly   modify sulfhydryl residues of proteins through S-nitrosylation   and induce apoptosis. We studied 3 NO-NSAIDs having a different   NSAID, spacer, and NO-releasing moiety. In vitro: aspirin,   NO-ASA, naproxen, and NO-naproxen inhibited HT-29 human colon   cancer cell growth, the IC(50)s being >5000, 192±6, 2800±210   and 95±5μM at 24h, respectively. NO-Aspirin and NO-naproxen   reduced NF-κB protein levels, and activated caspase-3 enzyme in a   dose- and time-dependent manner. Based on the biotin switch   assay, NO-ASA and NO-naproxen S-nitrosylated NF-κB p65 in a   time-dependent manner. Pretreatment of the cells with   carboxy-PTIO, abrogated the S-nitrosylation of NF-κB p65. In   vivo: rats treated with NO-ASA, NONO-ASA, and NO-naproxen showed   S-nitrosylation of NF-κB p65 in the stomach tissue, increases in   plasma TNF-α, and reductions in mucosal PGE(2) levels. These data   provide a mechanistic role for NO and a rational for the   chemopreventive effects of NO-NSAIDs.

  Address (URL): http://

 

Attachments

    Outcomes