Selected Statins as Dual Antiproliferative-Antiinflammatory Compounds

Area of Science:

• Pharmacology
• Oncology
• Biochemistry

Background:

• Lipophilic statins possess dual bioefficacies, including cytotoxicity and anti-inflammatory properties.
• These effects are hypothesized to correlate with the chelation of 3,5-dihydroxyheptanoic acid.

Purpose of the Study:

• To screen lipophilic-acid chelating statins for in vitro proliferation inhibition and nitric oxide (NO)-radical scavenging capacities.
• To evaluate the safety and efficacy spectrum of selected statins in various cancer cell lines and fibroblasts.

Main Methods:

• In vitro screening of 9 lipophilic statins for cytotoxicity and anti-inflammatory effects.
• Assessment of proliferation inhibition (IC50) and NO-radical scavenging in cancer cell lines (SW620, HT29, HCT116, Caco2, T47D, MCF7, PANC1) and PDL fibroblasts.
• Determination of selectivity indices for safety.

Main Results:

• Cerivastatin exhibited significant antitumorigenesis with IC50 values <50 µM across multiple cancer cell lines and potent anti-inflammatory activity without affecting macrophages.
• Lovastatin, atorvastatin, and rosuvastatin also displayed notable cytotoxicity (IC50 <20-50 µM) in various cancer cell lines.
• Pravastatin showed moderate cytotoxicity (IC50 <50 µM) in specific cancer cell lines, with higher values in others.

Conclusions:

• Cerivastatin demonstrates exceptional dual efficacy, warranting further investigation for novel scaffold development.
• Optimizing cerivastatin's molecular action mechanisms could enhance its potential in chemotherapy and cancer prevention strategies.