RESUMO
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 < .001 vs. cisplatin 0.07 µM IC50 value). Atorvastatin exhibited an equipotency to cisplatin's T47D growth inhibition (34.6 µM vs. 34.59 µM; p > .05). Levofloxacin as well as ciprofloxacin superbly superseded the antineoplastic cisplatin activity against the K562 cell line (respective IC50 values [µM] 10.4 and 19.5 vs. 29.3; p < .05-<.01). Gemifloxacin and lansoprazole had comparable antiproliferation in K562 to cisplatin's (respective IC50 values [µM] 34.9 and 36.3 vs. 29.3; 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 < .01-.001). Evidently, omeprazole, pioglitazone, gemifloxacin, and indomethacin were of comparable anti-inflammation potencies (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.
