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 IC50 values of 40nM (SW620), 110nM (HT29), 2.9 µM (HCT116), 6µM (SW480), and most notably 38µM (<50 µM, in Caco2). Exclusively cerivastatin exerted antitumorigenesis IC50 values <50 µM in all T47D, MCF7 and PANC1 72h cultures. In statins with greater antiinflammation affinity than indomethacin's; lovastatin had cytotoxicity IC50 values <20 µM in SW620<HT29<ACT116100 µM in Caco2. Atorvastatin was found of viability reduction IC50 value <20 µM in HCT11650µM in T47D, MCF7 and PANC1. Rosuvastatin had antineoplastic IC50 values (<50 µM) in SW620<SW48050 µM in remaining colorectal, breast and pancreatic cancer cell lines. In statins with appreciable antiinflammation but reasonably lower affinity than indomethacin's and cytotoxicity IC50 values >50µM in T47D, MCF7 and PANC1; pravastatin had viability reduction IC50 values <50µM in HT2950 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.