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J Herbmed Pharmacol. 2026;15(3): 398-406.
doi: 10.34172/jhp.53885
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Original Article

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

Ali Serat 1,2 ORCID logo, Nader Bagheri 3 ORCID logo, Pouyan Zandi 1,2 ORCID logo, Reza Yarahmadi 1,2 ORCID logo, Zahra Yazdani Chamheydari 4 ORCID logo, Seyed Abbas Mirzaei 1 ORCID logo, Hadi Raeisi Shahraki 5 ORCID logo, Hossein Teimori 1* ORCID logo

1 Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
2 Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran
3 Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
4 Department of Genetics, Faculty of Biological Sciences and Technology, Shahid Ashrafi Esfahani University, Isfahan, Iran
5 Department of Epidemiology and Biostatistics, School of Health, Shahrekord University of Medical Sciences, Shahrekord, Iran
*Corresponding Author: Hossein Teimori, Email: hteimori@skums.ac.ir

Abstract

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.


Implication for health policy/practice/research/medical education:

This study offers preliminary evidence linking eugenol exposure to reduced cell viability and modulated PRKAA1 mRNA expression in breast cancer, suggesting a potential role for this plant-derived compound in cancer research. These findings support further translational research into the use of natural bioactive compounds as exploratory candidates for modulating cancer cell metabolism. From a research and medical education perspective, this work highlights the importance of distinguishing between transcript-level associations and definitive mechanistic pathways. Ultimately, these results provide a conceptual foundation for future studies to validate eugenol’s effects at the protein and functional levels, ensuring a more comprehensive understanding of its potential therapeutic relevance.

Please cite this paper as: Serat A, Bagheri N, Zandi P, Yarahmadi R, Yazdani Chamheydari Z, Mirzaei SA, et al. The role of eugenol in modulating PRKAA1 expression and cellular energy homeostasis in breast cancer. J Herbmed Pharmacol. 2026;15(3):398-406. doi: 10.34172/jhp.53885.

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