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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
|---|---|
| Enthalten in: |
Asian Pacific journal of cancer prevention : APJCP - 23(2022), 12 vom: 01. Dez., Seite 4047-4062 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Haj Hussein, Buchra [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.01.2023 Date Revised 02.03.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.31557/APJCP.2022.23.12.4047 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a BACKGROUND: We hypothesized that superlative dual cytotoxicity-antiinflammtion bioefficacies of 9 selected lipophilic statins correlate to their chelation effect of 3,5-dihydroxyheptanoic acid | ||
| 520 | |a METHODOLOGY: Lipophilic-acid chelating statins have been screened for in vitro duality of proliferation inhibition and NO-radical scavenging capacities | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSION: Among the rest, cerivastatin warrants further novel scaffold development to maximize efficacy and optimal molecular action mechanisms of chemotherapy/prevention | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Statins | |
| 650 | 4 | |a Sulforhodamine B- Cisplatin | |
| 650 | 4 | |a cancer and Chelation | |
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| 700 | 1 | |a Arabiyat, Shereen |e verfasserin |4 aut | |
| 700 | 1 | |a Ikhmais, Balqis |e verfasserin |4 aut | |
| 700 | 1 | |a Alalawi, Sundus |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Qirim, Tariq |e verfasserin |4 aut | |
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