The role of eugenol in modulating PRKAA1 expression and cellular energy homeostasis in breast cancer

Introduction: Eugenol, a natural phenolic compound obtained from clove and cinnamon, has been reported to show anticancer properties in breast cancer models. Metabolic reprogramming is a hallmark of breast cancer and can be regulated by AMPK. The PRKAA1 gene encodes the catalytic subunit of AMPKα1. This study aimed to investigate the effects of eugenol on cell viability and PRKAA1 expression in human breast cancer cell lines. PRKAA1 expression patterns and prognostic relevance in breast cancer patient datasets were also analyzed. Methods: RNA-seq data from ENCORI/StarBase were employed to compare PRKAA1 expression in tumor and normal breast tissues. Kaplan–Meier analysis evaluated possible associations between PRKAA1 expression levels and overall survival. MCF-7 and MDA-MB-231 cell lines were treated with eugenol, and cell viability was assessed using the MTT assay. PRKAA1 expression levels were measured by RT-qPCR after eugenol treatment and compared with controls. Results: Bioinformatics analysis showed lower PRKAA1 expression in breast cancer compared with normal breast samples (P = 4.3e-24, false discovery rate [FDR] = 4.4e-23). Survival analysis showed no significant association between PRKAA1 expression and overall survival in breast cancer patients (P = 0.69; hazard ratio [HR] = 1.07). Eugenol reduced the viability of both cell lines and showed greater toxicity with increasing concentrations and exposure time. Eugenol treatment downregulated PRKAA1 expression (P < 0.001). Conclusion: Eugenol treatment altered PRKAA1 expression in both cell lines. These findings may suggest a potential link between eugenol induced cytotoxicity and changes in energy homeostasis genes; however, further studies are required to clarify the role of AMPK signaling in this context.