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

Che-Yi Chao, Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 41354, Taiwan,
Woei-Cheang Shyu, Graduate Institute of Biomedical Science, China Medical University, Taichung 40604, Taiwan
Chih-Lung Lin, Department of Neurosurgery, Asia University Hospital, Taichung 41354, Taiwan
En-Pei Isabel Chiang, Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan
Yueh-Hsiung Kuo, Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, 19 China Medical University, Taichung 40604
Feng-Yao Tang, China Medical University Taichung, TAIWANFollow

Abstract

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.

Recommended Citation

Chao, Che-Yi; Shyu, Woei-Cheang; Lin, Chih-Lung; Chiang, En-Pei Isabel; Kuo, Yueh-Hsiung; and Tang, Feng-Yao () "Decyl caffeate inhibits the proliferation of human triple-negative breast cancer cells," BioMedicine: Vol. 16 : Iss. 1 , Article 4.
DOI: 10.37796/2211-8039.1695