Selected pharmacotherapy agents as antiproliferative and anti‐inflammatory compounds

The repurposing of safe therapeutic drugs has emerged as an alternative approach to rapidly identify effective, safe, and conveniently available therapeutics to treat/prevent cancer. Therefore, it was hypothesized that acidic chelator drugs could have a genuine potential as antiproliferative agents....

Full description

Saved in:
Bibliographic Details
Published in:Drug development research 2020-06, Vol.81 (4), p.470-490
Main Authors: AlKhalil, Mthanna, Al‐Hiari, Yusuf, Kasabri, Violet, Arabiyat, Shereen, Al‐Zweiri, Muhammad, Mamdooh, Noor, Telfah, Ahmad
Format: Article
Language:English
Subjects:
antiproliferation
Antiproliferatives
anti‐inflammation
Atorvastatin
Biotechnology
Breast
Cancer
Cervix
Chemotherapy
Ciprofloxacin
Cisplatin
Clopidogrel
commercial agents
Cytotoxicity
Drug therapy
Drugs
Fibroblasts
Fluoroquinolones
Gemifloxacin
Growth inhibition
Indomethacin
Inflammation
Leukemia
Levofloxacin
Lipopolysaccharides
Macrophages
Nicotinic acid
Omeprazole
Pancreas
Pioglitazone
Piroxicam
Proton pump inhibitors
Statins
Toxicity
Tumor cell lines
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The repurposing of safe therapeutic drugs has emerged as an alternative approach to rapidly identify effective, safe, and conveniently available therapeutics to treat/prevent cancer. Therefore, it was hypothesized that acidic chelator drugs could have a genuine potential as antiproliferative agents. Based on their pKa, the selected 15 acidic drugs of eight classes—namely sulfonylureas, proton pump inhibitors, fluoroquinolones, nonsteroidal anti‐inflammatory agents, thiazolidinediones, thienopyridines, statins, and nicotinic acid—were assayed for anticancer HTS against the lung A549, skin A375, breast MCF7 and T47D, pancreatic PANC1, cervical HeLa, and leukemia K562 cancer cell lines and normal fibroblasts. Lipopolysaccharide‐prompted inflammation in RAW264.7 macrophages was the potential anticancer mechanism. Atorvastatin exerted remarkably superior cytotoxicity against A375.2S (IC50 value 0.02 μM p  .05). The selected agents lacked cytotoxicity in the panel of MCF7, HeLa, A549, or Panc1 cancer cells. Most notably, LPS prompted RAW264.7 macrophages, atorvastatin, piroxicam, clopidogrel, esomeprazole, and lansoprazole were of higher anti‐inflammation potency than indomethacin (p  .05). Collectively, this work reveals acidic chelator drugs (atorvastatin, gemifloxacin, and lansoprazole with dual anti‐inflammation and antiproliferation propensities) as authentic agents for the repurposing approach in anticancer chemotherapy/prevention.
ISSN:0272-4391
1098-2299
DOI:10.1002/ddr.21640