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.
