The role of eugenol in modulating PRKAA۱ 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 PRKAA۱ gene encodes the catalytic subunit of AMPKα۱. This study aimed to investigate the effects of eugenol on cell viability and PRKAA۱ expression in human breast cancer cell lines. PRKAA۱ expression patterns and prognostic relevance in breast cancer patient datasets were also analyzed. Methods: RNA-seq data from ENCORI/StarBase were employed to compare PRKAA۱ expression in tumor and normal breast tissues. Kaplan–Meier analysis evaluated possible associations between PRKAA۱ expression levels and overall survival. MCF-۷ and MDA-MB-۲۳۱ cell lines were treated with eugenol, and cell viability was assessed using the MTT assay. PRKAA۱ expression levels were measured by RT-qPCR after eugenol treatment and compared with controls. Results: Bioinformatics analysis showed lower PRKAA۱ expression in breast cancer compared with normal breast samples (P = ۴.۳e-۲۴, false discovery rate [FDR] = ۴.۴e-۲۳). Survival analysis showed no significant association between PRKAA۱ expression and overall survival in breast cancer patients (P = ۰.۶۹; hazard ratio [HR] = ۱.۰۷). Eugenol reduced the viability of both cell lines and showed greater toxicity with increasing concentrations and exposure time. Eugenol treatment downregulated PRKAA۱ expression (P < ۰.۰۰۱). Conclusion: Eugenol treatment altered PRKAA۱ 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.