An In Vitro Investigation of the Antiproliferative and Antimetastatic Effects of Levosimendan: Potential Drug Repurposing for Cervical Cancer

Abstract

Cervical cancer presents a significant challenge to the global health of women. Despite substantial advances in human papillomavirus (HPV)-related cervical cancer vaccines, non-HPV-related cervical cancer is still waiting novel therapeutic options. Drug repurposing has provided a promising approach to improve cancer therapy in recent years. Our study aimed to explore the potential in vitro antineoplastic effects of levosimendan on cervical cancer cells. The antiproliferative effects of levosimendan were investigated on cervical cancer cells using a standard MTT assay. Fluorescent double staining was performed to identify its ability to induce apoptosis and necrosis. The possible mechanism of action of levosimendan was explored using cell-cycle analysis. Furthermore, antimetastatic effects were investigated using a wound-healing assay and a Boyden chamber assay. Our results revealed that levosimendan exhibited the highest growth-inhibitory effect in the HPV-negative C33A cell line. However, the effects were modest compared to the standard agent, cisplatin. Cell-cycle analysis detected that levosimendan can induce cell-cycle arrest in C33A cells by increasing the G1 and G2/M phases, decreasing the S phase, and enhancing the hypodiploid subG1 population. Levosimendan inhibited cell migration and invasion in a concentration-dependent manner. As levosimendan showed antimetastatic efficacy, it could be considered for repurposing to contribute to overcoming resistance to therapy in cervical cancer.