A Novel Endophytic Fungus, Alternaria semiverrucosa , and Its Ethyl Acetate Extract Inhibit the Proliferation, Migration, and Invasion of Cervical Cancer Cells

ABSTRACT

The present study aimed to identify the endophytic fungus ZZ‐HZ‐13 from Taxus chinensis var. marei and to investigate its biological activity. A novel species, Alternaria semiverrucosa (ZZ‐HJ‐13), was identified through morphological analysis combined with multigene phylogeny. The ethyl acetate extract (EAE) of A. semiverrucosa fermentation products demonstrated inhibitory effects on cervical cancer cells. Increasing concentrations of EAE caused marked morphological changes and higher inhibition rates in cervical cancer cells. After 48 h, the apoptosis rate of the cells significantly increased with increasing EAE concentration. In addition, the proportion of cells in the G ₁ phase decreased, while the proportion in the G ₂ phase increased significantly, indicating cell cycle arrest. Cell invasion and migration were also inhibited in a concentration‐dependent manner. Protein expression analysis revealed a significant upregulation of proapoptotic proteins, including Bax, cleaved caspase‐3, and cleaved caspase‐9, and of the cell cycle‐associated regulatory protein p21. Conversely, the expression levels of the antiapoptotic protein Bcl‐2 and the cell migration‐related proteins MMP1 and MMP9 were markedly decreased. In vivo experiments further demonstrated that EAE can suppress tumor growth in a mouse xenograft model. In conclusion, EAE derived from A. semiverrucosa demonstrates significant inhibitory effects on the proliferation of cervical cancer cells.