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RSS FeedsIJMS, Vol. 20, Pages 3074: Antiproliferative Activity of Pt(IV) Conjugates Containing the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Ketoprofen and Naproxen + (International Journal of Molecular Sciences)

 
 

24 june 2019 21:02:25

 
IJMS, Vol. 20, Pages 3074: Antiproliferative Activity of Pt(IV) Conjugates Containing the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Ketoprofen and Naproxen + (International Journal of Molecular Sciences)
 


Cisplatin and several non-steroidal anti-inflammatory drugs (NSAIDs) have been proven to act synergistically or at least additively on several tumor cell lines. Dual-action cisplatin-based Pt(IV) combos containing ketoprofen and naproxen offer good antiproliferative performance on a panel of human tumor cell lines, including a malignant pleural mesothelioma (MPM) one, a very chemoresistant tumor. The main reason of the increased activity relies on the enhanced lipophilicity of these Pt(IV) conjugates that in turn promotes increased cellular accumulation. A quick Pt(IV)->Pt(II) reduction generates the active cisplatin metabolite. The NSAID adjuvant action seems to be almost independent from cyclooxygenase-2 (COX-2) expression in the tumor cells under investigation (lung A-549, colon HT-29, HCT 116, SW480, ovarian A2780, and biphasic MPM MSTO-211H), but it seems to rely (at least in part) on the activation of the NSAID activated gene, NAG-1 (a member of the transforming growth factor beta, TGF-?, superfamily), which has been suggested to be involved in NSAID antiproliferative activity.


 
85 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
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