Anti-Proliferative Effect of Statins Is Mediated by DNMT1 Inhibition and p21 Expression in OSCC Cells.
Rachmad Anres DongoranKai-Hung WangTsung-Jen LinTa-Chun YuanChin-Hung LiuPublished in: Cancers (2020)
Statins, also known as HMG-CoA reductase inhibitors, are a class of cholesterol-lowering drugs and their anti-cancer effects have been studied in different types of malignant diseases. In the present study, we investigated the anti-proliferative effects of statins, including cerivastatin and simvastatin, on oral squamous cell carcinoma (OSCC) cells. Our data showed that statins inhibited the proliferation of three OSCC cell lines in a dose-dependent manner and this growth inhibition was confirmed through G0/G1 cell cycle arrest. Accordingly, we found the upregulation of p21 and downregulation of cyclin-dependent kinases, including CDK2, CDK4, and CDK6, in the statin-treated cells. Importantly, we clearly showed that statins were able to inhibit the expression of DNA methyltransferase 1 (DNMT1) and further promote the expression of p21. Taken together, our data demonstrated that the anti-proliferative effect of statins is mediated by suppressing DNMT1 expression, thus promoting p21 expression and leading to G0/G1 cell cycle arrest in OSCC cells.
Keyphrases
- cell cycle arrest
- cell death
- poor prognosis
- pi k akt
- cardiovascular disease
- induced apoptosis
- signaling pathway
- dna methylation
- cell proliferation
- cell cycle
- long non coding rna
- binding protein
- coronary artery disease
- electronic health record
- oxidative stress
- machine learning
- high resolution
- single molecule
- deep learning
- low density lipoprotein
- atomic force microscopy