Selected Statins as Dual Antiproliferative-Antiinflammatory Compounds

Haj Hussein, Buchra; Kasabri, Violet; Al-Hiari, Yusuf; Arabiyat, Shereen; Ikhmais, Balqis; Alalawi, Sundus; Al-Qirim, Tariq

doi:10.31557/APJCP.2022.23.12.4047

Selected Statins as Dual Antiproliferative-Antiinflammatory Compounds

Document Type : Research Articles

Authors

¹ School of Pharmacy, University of Jordan, Amman 11942, Queen Rania Street, Jordan.

² Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P. O. Box 130, Amman 11733, Jordan.

³ Salt College, AlBalqa Applied University, Salt 19117, Jordan.

10.31557/APJCP.2022.23.12.4047

Abstract

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.

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