Alpinetin inhibits proliferation and migration of ovarian cancer cells via suppression of STAT3 signaling

Natural bioactive components are increasingly being applied in cancer research. Alpinetin is a type of natural flavonoid primarily derived from Alpinia katsumadai Hayata, which exhibits anti-bacterial and anti-inflammatory properties. Therefore, it may possess anticancer potential and be employed therapeutically for different diseases. The aim of the present study was to investigate the anticancer effects of alpinetin on the SKOV3 ovarian cancer cell line. The effect of alpinetin treatment on SKOV3 cell proliferation, apoptosis, spheroid and colony formation were measured using Cell Counting kit-8, cell apoptosis, 3D spheroid and colony formation assays, respectively. Analysis of the cell cycle was performed using flow cytometry. Western blot analysis was used to determine the protein expression levels of B-cell lymphoma (Bcl)-2, Bcl-2-associated X protein, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), cyclin D1, cyclin-dependent kinase (CDK) 4, CDK6, signal transducer and activator of transcription (STAT) 3, phosphorylated (p)-STAT3, c-myc, survivin, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, matrix metalloproteinase (MMP)-2 and MMP-9. In addition, a wound healing assay was used to determine cancer cell migration. The results revealed alpinetin suppressed cell viability and induced apoptosis of SKOV3 cells in a dose- and time-dependent manner, and cells were arrested in the G(1) phase. Alpinetin treatment upregulated protein expression levels of Bax, cleaved caspase-3 and PARP, and downregulated protein expression levels of Bcl-2, cyclin D1, CDK4 and CDK6. Alpinetin also inhibited cell migration, through increased protein expression levels of TIMP-1 and TIMP-2, and decreased protein expression levels of MMP-2 and MMP-9. Alpinetin also significantly suppressed colony and spheroid formation by SKOV3 cells. In addition, the STAT3 pathway was suppressed as demonstrated by downregulation of p-STAT3 and reduced expression of downstream factors, including c-myc and survivin. Overall, these results indicated that alpinetin may have anticancer effects on human ovarian cancer by inhibiting the STAT3 signaling pathway.