In Vitro Investigation of the Antiproliferative and Antimetastatic Effects of Atorvastatin: A Focus on Cervical and Head and Neck Cancers

<b>Background/Objectives</b>: In spite of substantial treatment progress, cancer persists as a leading health challenge. With the slow advancement in developing new anticancer agents, drug repurposing provides a promising strategy to enhance cancer therapy. This study investigates the antiproliferative and antimetastatic properties of two 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, atorvastatin and rosuvastatin, which represent lipophilic and hydrophilic statins, respectively. <b>Methods</b>: Growth inhibition was evaluated in a panel of human cancer cells using the standard MTT assay. Apoptotic effects were determined through flow cytometry, caspase-3 activity assay, mitochondrial membrane potential assessment, and Hoechst/Propidium iodide fluorescent double staining. Migration and invasion assays were conducted using wound-healing and Boyden chamber assays, respectively. <b>Results:</b> Atorvastatin demonstrated more pronounced growth-inhibitory effects than rosuvastatin, with the IC₅₀ values in the range of 2.57-61.01 µM. Atorvastatin exhibited both biochemical and morphological indicators of apoptosis. Flow cytometry revealed cell cycle disruptions and increased sub-G1 apoptotic populations in HPV-positive oral squamous carcinoma cells (UPCI-SCC-154) and HPV-negative cervical cancer cells (C33A). Atorvastatin also significantly inhibited cell migration and invasion in the tested cell lines. <b>Conclusions</b>: Our results highlight the promising anticancer potential of atorvastatin in cervical cancer and oral squamous carcinoma cells. However, these findings are limited to in vitro models and warrant further in vivo validation.