α-hederin inhibits cervical cancer progression by inducing DNA damage-dependent cell cycle blockade and apoptosis.

Abstract

Background: Cervical cancer incidence has not decreased significantly despite widespread use of HPV vaccines and screening measures.

Purpose: This study explored the potential of α-Hederin in the treatment of cervical cancer.

Methods: CCK8, EdU staining assay, flow cytometry were conducted for apoptosis, cell cycle, ROS, and mitochondrial membrane potential. Mechanism effects of α-hederin on cervical cancer cells were investigated using transcriptome sequencing, bioinformatics analysis, and single-cell sequencing. Further in-depth detection of key proteins with western blot, immunofluorescence, overexpression of CHK1 gene, DNA damage inhibitors, and NAC inhibitors were performed to study the regulation of the cell cycle. In vivo nude mice tumorigenicity experiments and metabolomics analysis of the tumor tissue were also performed.

Results: α-Hederin significantly inhibited SiHa and HeLa cell growth, promoted apoptosis, and inhibited migration and invasion of cervical cancer cells. Sequencing and bioinformatics analysis revealed that α-hederin mainly regulated cell cycle, DNA replication, P53, and other signaling pathways to inhibit the proliferation of cervical cancer cells and inhibited the G2M phase of the cell cycle, mainly by suppressing CDK1 and CyclinB expression. α-hederin may use ATM-CHK1-CDC25B/CDC25C and ATM-P53-P21 to regulate CDK1/Cycline B activity. Inhibition of this action significantly promoted G2M phase block. In vivo experiment indicated that the drug can effectively inhibit cervical cancer growth.

Conclusion: α-hederin may be an effective drug to inhibit cervical cancer and has a good development prospect.