Selected Statins as Dual Antiproliferative-Antiinflammatory Compounds

BACKGROUND: We hypothesized that superlative dual cytotoxicity-antiinflammtion bioefficacies of 9 selected lipophilic statins correlate to their chelation effect of 3,5-dihydroxyheptanoic acid. METHODOLOGY: Lipophilic-acid chelating statins have been screened for in vitro duality of proliferation inhibition and NO-radical scavenging capacities. Results: Their spectrum of selectivity indices for safety in PDL fibroblasts -based 72h incubations was reported. Surprisingly despite its lack on macrophages LPS-triggered inflammation over 5-200 µM and unlike the 8 statins; cerivastatin had growth inhibition IC(50) values of 40nM (SW620), 110nM (HT29), 2.9 µM (HCT116), 6µM (SW480), and most notably 38µM (<50 µM, in Caco(2)). Exclusively cerivastatin exerted antitumorigenesis IC(50) values <50 µM in all T47D, MCF7 and PANC1 72h cultures. In statins with greater antiinflammation affinity than indomethacin’s; lovastatin had cytotoxicity IC(50) values <20 µM in SW620<HT29<ACT116<SW480 and >100 µM in Caco(2). Atorvastatin was found of viability reduction IC(50 )value <20 µM in HCT116<SW620. Simvastatin exerted growth inhibition IC(50) values <20 µM in HT29< SW620<SW480 and MCF7. Rosuvastatin, pitavastatin and fluvastatin proved equipotency to indomethacin but cytotoxicity IC(50) values >50µM in T47D, MCF7 and PANC1. Rosuvastatin had antineoplastic IC(50) values (<50 µM) in SW620<SW480<MCF7. Pitavastatin was ascribed cytotoxicity IC(50) values (<50µM) in HT29<SW620<HCT116<SW480. Fluvastatin had antiproliferation IC(50) values (<50µM) in SW620< HT29<SW480<HCT116, and the rest were >50 µM in remaining colorectal, breast and pancreatic cancer cell lines. In statins with appreciable antiinflammation but reasonably lower affinity than indomethacin’s and cytotoxicity IC(50) values >50µM in T47D, MCF7 and PANC1; pravastatin had viability reduction IC(50) values <50µM in HT29<HCT116. Mevastatin was reported for growth inhibition IC(50) values <50µM in HT29<SW620<HCT112<SW480. Antitumorigenesis IC(50 )values>50 µM were for statins in remaining colorectal cancer cell lines, breast cancer and pancreatic cancer cell lines.Conclusion: Among the rest, cerivastatin warrants further novel scaffold development to maximize efficacy and optimal molecular action mechanisms of chemotherapy/prevention.