Atorvastatin Downregulates In Vitro Methyl Methanesulfonate and Cyclophosphamide Alkylation-Mediated Cellular and DNA Injuries

• Published in: Oxidative medicine and cellular longevity 2018-01, Vol.2018 (2018), p.1-11
• Main Authors: Alessandra Fortes Aiub, Claudia, Soeiro, Maria N. C., Justo, Graça, Christoni, Larissa S. A., Araujo-Lima, Carlos F., Felzenszwalb, Israel
• Format: Article
• Language: English
• Subjects: Accountants; Alkylating Agents - chemistry; Alkylating Agents - pharmacology; Alkylation; Antilipemic agents; Atorvastatin Calcium - chemistry; Atorvastatin Calcium - pharmacology; Cancer; Cell Cycle Checkpoints - drug effects; Cell Nucleus - chemistry; Cell Nucleus - drug effects; Cyclophosphamide; Cyclophosphamide - chemistry; Cyclophosphamide - pharmacology; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - drug effects; DNA methylation; Down-Regulation - drug effects; Drug resistance; Enzymes; Glucose; Hep G2 Cells; Humans; Malaria; Metabolism; Methyl Methanesulfonate - chemistry; Methyl Methanesulfonate - pharmacology; Methylation; Mutation; Prevention; Regression analysis; Salmonella enterica - drug effects; Salmonella enterica - genetics; Toxicology
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2018/7820890

Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, and this class of drugs has been studied as protective agents against DNA damages. Alkylating agents (AAs) are able to induce alkylation in macromolecules, causing DNA damage, as DNA methylation. Our objective was to evaluate atorvastatin (AVA) antimutagenic, cytoprotective, and antigenotoxic potentials against DNA lesions caused by AA. AVA chemopreventive ability was evaluated using antimutagenicity assays (Salmonella/microsome assay), cytotoxicity, cell cycle, and genotoxicity assays in HepG2 cells. The cells were cotreated with AVA and the AA methyl methanesulfonate (MMS) or cyclophosphamide (CPA). Our datum showed that AVA reduces the alkylation-mediated DNA damage in different in vitro experimental models. Cytoprotection of AVA at low doses (0.1–1.0 μM) was observed after 24 h of cotreatment with MMS or CPA at their LC50, causing an increase in HepG2 survival rates. After all, AVA at 10 μM and 25 μM had decreased effect in micronucleus formation in HepG2 cells and restored cell cycle alterations induced by MMS and CPA. This study supports the hypothesis that statins can be chemopreventive agents, acting as antimutagenic, antigenotoxic, and cytoprotective components, specifically against alkylating agents of DNA.