Decyl caffeate inhibits the proliferation of human triple-negative breast cancer cells

Background: Over recent decades, considerable attention has been directed toward the discovery of novel compounds capable of targeting survival-related signaling networks as therapeutic candidates for triple-negative breast cancer (TNBC). Central to TNBC pathobiology are the Akt/mTOR and MAPK/ERK signaling axes, both contribute to tumor progression and therapeutic resistance. Caffeic acid (CA), a naturally derived phenolic compound with anti-inflammatory activity, has previously been investigated for its anti-cancer potential. Purpose: In the present study, we explored the therapeutic value of newly synthesized CA derivatives in TNBC models using both cellular and animal-based systems. Methods: The anti-tumor efficacy of these CA derivatives was examined through a series of functional assays, including cell proliferation, clonogenicity, cell cycle profiling, apoptosis quantification, ELISA, western blotting, and histopathological analysis. Results: Among the tested derivatives, decyl caffeate (DC) demonstrated the most pronounced inhibitory effects on TNBC cell growth, significantly decreasing viability, colony formation, and enhancing cisplatin responsiveness (P < 0.05). DC induced G2/M phase arrest in MDA-MB-468 cells, accompanied by suppression of cyclin B1 and CDK1 expression. In addition, DC downregulated both total and phosphorylated c- Myc and reduced secretion of TGF-α, a key ligand for EGFR. Apoptotic responses were evident through upregulation of Bax, cleaved caspase-3, and cleaved-PARP. Mechanistic analysis revealed that these effects were mediated via concurrent inactivation of the Akt/mTOR and MAPK/ERK signaling pathways. Oral administration of DC in a murine TNBC xenograft model significantly suppressed tumor growth in vivo. Conclusion: Altogether, these results highlight DC as a promising bioactive compound that targets essential oncogenic pathways in TNBC and support its potential for further preclinical development.