IKK inhibitor
CAS锛?9-57-6
鍒嗗瓙寮忥細C7H7NO3
鍒嗗瓙閲忥細153.14
绾害锛?8%
瀛樺偍锛歋tore at -20掳C

Background:

5-Aminosalicylic acid (Mesalamine) acts as a specific PPAR纬 agonist and also inhibits p21-activated kinase 1 (PAK1) and NF-魏B.

5-Aminosalicylic acid (5-ASA) is a specific agonist for PPAR纬, and only PPAR纬 but not PPAR伪 or PPAR未 induces p65 degradation. 5-Aminosalicylic acid induces degradation of p65 protein indicative of PPAR纬's E3 ubiquitin ligase activity. 5-Aminosalicylic acid also inhibits PAK1 at the mRNA level which is suggestive of an additional mechanism independent of PPAR纬 ligand activation. 5-Aminosalicylic acid blocks NF-魏B in intestinal epithelial cells (IECs) through inhibition of PAK1[1]. Pretreatment with 5-Aminosalicylic acid (5-ASA) or Nimesulide at different concentration (10-1000 渭mol/L) for 12-96 h, inhibits the growth of HT-29 colon carcinoma cells in a dose and time-dependent manner. However, the suppression of 5-Aminosalicylic acid or Nimesulide has no statistical significance. The growth of HT-29 colon carcinoma cells is inhibited dose-dependently when pretreated with different doses of combined 5-Aminosalicylic acid and Nimesulide. Combined 5-Aminosalicylic acid (final concentration 100 渭M) and Nimesulide (final concentration 10-1000 渭M) inhibits the proliferation of HT-29 colon carcinoma cells in a dose-dependent manner, being more potent than corresponding dose of Nimesulide. Similarly, combined Nimesulide (final concentration 100 渭M) and 5-Aminosalicylic acid (final concentration 10-1000 渭M) also inhibits the proliferation of these cells dose-dependently, being more potent than corresponding dose of 5-Aminosalicylic acid[2].

5-Aminosalicylic acid (5-ASA) has an antineoplastic effect in a xenograft tumor model. To evaluate the in vivo antineoplasic effect of 5-Aminosalicylic acid, SCID mice engrafted with HT-29 colon cancer cells are treated daily for 21 consecutive days with 5-Aminosalicylic acid at 50 mM. At the end of the treatment, a reduction of 80-86% of tumor weight and volume is observed in SCID mice receiving 5-Aminosalicylic acid compared with control mice or mice treated with GW9662 alone. The antineoplastic effect of 5-Aminosalicylic acid is already detectable after 10 days of 5-Aminosalicylic acid treatment. Similar results are obtained with mice treated with 5-Aminosalicylic acid at 5 mM. Antitumorigenic effect of 5-Aminosalicylic acid is completely abolished at 21 days by simultaneous intraperitoneal administration of GW9662. Thus, the observed antineoplastic effect of 5-Aminosalicylic acid is at least partially dependent on PPAR纬[3].

鍙傝€冩枃鐚?
[1]. Dammann K, et al. PAK1 modulates a PPAR纬/NF-魏B cascade in intestinal inflammation. Biochim Biophys Acta. 2015 Oct;1853(10 Pt A):2349-60.
[2]. Rousseaux C, et al. The 5-aminosalicylic acid antineoplastic effect in the intestine is mediated by PPAR纬. Carcinogenesis. 2013 Nov;34(11):2580-6.
[3]. Fang HM, et al. 5-aminosalicylic acid in combination with Nimesulide inhibits proliferation of colon carcinoma cells in vitro. World J Gastroenterol. 2007 May 28;13(20):2872-7.