Selected pharmacotherapy agents as antiproliferative and anti‐inflammatory compounds

Abstract

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. Lipopolysaccharideprompted 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 Levofloxacin as well as ciprofloxacin superbly superseded the antineoplastic cisplatin activity against the K562 cell line (respective IC50 values [μM] 10.4 and 19.5 vs. 29.3; p 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 antiinflammation 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. K E Y W O R D S anti-inflammation, antiproliferation, commercial agents

Levofloxacin Might be Safe to use for OSCC Patients

“…In another study, researchers evaluated the anticancer activities of 15 acidic drugs selected from 8 classes, including uoroquinolones and nonsteroidal anti-in ammatory agents, on different cancer cell lines and reported that levo oxacin has selective cytotoxic activity on cancer cells. According to the study, while levo oxacin did not show any cytotoxic activity on healthy cell line used as a control, it exhibited signi cant antiproliferative activity on K562 chronic leukemia cells (AlKhalil et al 2020).…”

Effects of Proton Pump Inhibitors on Serum Calcium Level: A Study on Rabbit Model

“…The PPI are the inhibitor of H/K ATPase pump and worldwide used for the treatment of different gastrointestinal disorder. Omeprazole commonly prescribed in clinical setup for treatment of gastro esophageal reflux, acidity due usage of NSAID's drugs, peptic ulcer [17,18]. Some studies observed there is relation between long term usage of PPI with bone mineralization, calcium absorption [19].…”

Selected Statins as Dual Antiproliferative-Antiinflammatory Compounds

“…This work is a continuation of a recent research line on re-purposing drugs toward new activities or diseases. Importantly a significant high antiproliferative activity of atorvastatin on two cell lines A375.2S cell line and T47D cell line with IC 50 of 0.0156 µM and 34.59 µM respectively were revealed (AlKhalil et al, 2020). These data were further validated with other cell lines including colorectal cancer (CRC); fortifying the fact that atorvastatin has an apoptotic effect on cancer cells, particularly colorectal (CRC) and BC (in SW620 cells with IC 50 value accounting to 0.0018 ±0000 µM) and accordingly high safety (Mamdooh et al, 2019).…”