Abstract
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.
Highlights
Oral cancer is one of the most common cancers globally and oral squamous cell carcinoma (OSCC)represents 95% of all forms of it [1,2]
The results of the sulforhodamine B (SRB) assay were expressed as the percentage of cell proliferation using dimethyl sulfoxide (DMSO) treatment as the vehicle control group
The results suggest that statins could act as DNA methyltransferase 1 (DNMT1) inhibitors to promote the transcriptional activation of p21
Summary
Oral cancer is one of the most common cancers globally and oral squamous cell carcinoma (OSCC)represents 95% of all forms of it [1,2]. Oral cancer is one of the most common cancers globally and oral squamous cell carcinoma (OSCC). Excessive alcohol consumption, and chronic betel quid chewing are three major risk factors for the development of oral cancer. The therapeutic options, including surgery, radiation therapy, chemotherapy, targeted therapy, and immunotherapy applied in OSCC have expanded in scope and have brought about meaningful improvements in patient outcomes [5]. Toxicity, side effects, and tumor recurrence following treatment remain major clinical challenges in oral cancer [6]. Newer drugs and treatments are needed to overcome these challenges
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