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

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). 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%). 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. 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.