Influence of Caffeic Acid Phenethyl Ester on Osteoblastic Cell Behavior in Coculture With Breast Adenocarcinoma Cells.

Background/aim: Breast cancer is the leading cause of cancer-related death in women. The Wnt pathway, essential for osteogenesis, may help counteract tumor-induced bone damage. Caffeic acid phenethyl ester (CAPE), a natural polyphenol, shows anti-tumor, anti-inflammatory, and bone anabolic effects. This study aimed to evaluate the in vitro effects of CAPE (10 nM) on osteoblastic cells (Saos-2) cocultured with breast adenocarcinoma cells (AU565).

Materials and methods: ALP activity was assessed on days 5 and 10, mineralization on day 14, and gene expression (DKK1, SOST, TNFSF11, TNFSF11B) on days 5 and 10. Data were analyzed using the Kruskal-Wallis test (α=5%).

Results: On day 5, AU565 coculture reduced ALP activity in Saos-2 cells (p<0.05), which CAPE reversed (p<0.05). No differences were observed on day 10 (p>0.05). Mineralization was reduced by coculture and restored by CAPE (p <0.05). In AU565 cells, coculture upregulated DKK1, SOST, and TNFSF11 (p<0.05); CAPE downregulated SOST (day 5) and TNFSF11 (both days), upregulated TNFSF11B, and had no effect on DKK1. In Saos-2 cells, coculture increased all target genes (p<0.05); CAPE upregulated TNFSF11B (day 5), had no effect on other genes at that time, and downregulated DKK1, SOST, and TNFSF11 on day 10 (p<0.05), with no effect on TNFSF11B.

Conclusion: CAPE reduces Wnt pathway antagonists and osteoclastogenesis genes while restoring osteoblastic matrix calcification, supporting its potential to mitigate the effects of breast adenocarcinoma metastasis in bone tissue.