Fu Fang Gang Liu aqueous extract inhibits the proliferation of HeLa cells by causing deoxyribonucleic acid damage

Abstract

Ethnopharmacological relevanceFu Fang Gang Liu (FFGL) is an effective formula for treating wart proliferation caused by human papillomavirus (HPV) infection and has the potential to treat HPV-related cancers. However, scientific evidence of its anti-tumor activity against cervical cancer, the most common cancer caused by HPV, is lacking. Aim of the studyTo clarify the anti-tumor effect of an FFGL aqueous extract on human cervical cancer and its possible mechanism of cell cycle arrest in HeLa cells. Materials and methodsThe anti-proliferative effect of FFGL on cervical cancer cells was assessed using the cell counting kit-8 assay. The proportion of apoptotic cells, cell cycle distribution, and cell division rate were determined using flow cytometry. Quantitative proteomics was used to identify differentially expressed proteins after FFGL treatment, and bioinformatics analysis was used to identify key nodal proteins affected by FFGL. Immunofluorescence and western blot analyses were used to explore changes in the expression of related proteins in the cell cycle and DNA damage pathways to elucidate the potential mechanism of action of FFGL against HeLa cell proliferation. ResultsFFGL inhibited cervical cancer cell proliferation and caused cell cycle arrest. According to quantitative proteomics, CyclinB1 may play an important role in the anti-proliferative effect of FFGL on HeLa cells. Additional experiments showed that FFGL aqueous extract caused ATM-mediated DNA damage, further phosphorylated CHK2, led to the inactivation of Cdc25C, inhibited the activity of the CDK1/CyclinB1 complex, and resulted in cell cycle arrest. ConclusionsFFGL can inhibit cervical cancer cell proliferation. Furthermore, it can increase CDK1 phosphorylation, block the cell cycle by causing DNA damage, and inhibit HeLa cell proliferation.