Synergetic effect of doxorubicin and avenanthramide C on VDAC2/MTCH1 mitochondrial axis in breast cancer cells

Ehab M.M. Ali
Professor of Biochemistry, Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Sultan N. Sonbul
Assistant Professor of Molecular Biochemistry and Breast Cancer Pathology, Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Eman A. Almuhaini
Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Ayat B. Al-Ghafari
abalghafari@kau.edu.sa (Primary Contact)
Associate Professor of Biomedical Sciences
PDF

Abstract

Objectives: This study aims to evaluate the synergistic effects of doxorubicin (DOX) and the natural phenolic alkaloid avenanthramide C (AVC) on enhancing apoptosis in MCF-7 breast cancer (BC) cells, with a specific focus on the expression of mitochondrial proteins voltage-dependent anion channel 2 (VDAC2) and mitochondrial carrier homolog 1 (MTCH1) involved in apoptosis pathways.
Methods: MCF-7 cells were treated with various concentrations of DOX and AVC. The 50% inhibitory concentration (IC50) of DOX combined with AVC was evaluated in the MCF-7 cells using an MTT assay, while gene expression levels of Ki-67, MTCH1, and VDAC2 were assessed through real-time polymerase chain reaction. Apoptotic rates were measured using flow cytometry.
Results: DOX and AVC combination reduced the IC50 value by 2.1-fold compared to DOX alone, indicating enhanced cytotoxicity. Co-treatment significantly downregulated Ki-67 expression and increased apoptosis by 76% in cells treated with 3 μM DOX and 160 μM AVC. Gene expression analysis revealed a 4.8-fold increase in MTCH1 and a 15-fold increase in VDAC2 compared to DOX treatment alone.
Conclusion: The DOX-AVC combination demonstrated a potent synergistic effect, enhancing apoptosis in BC cells by modulating mitochondrial pathways. This approach may provide a promising strategy for reducing chemotherapy side effects in BC treatment. Further studies in pre-clinical models are warranted to explore its therapeutic potential.

Keywords:

Avenanthramide C Breast Cancer doxorubicin drug synergistic effect mitochondrial carrier homolog 1 voltage-dependent anion channel 2
Table of Contents
Ali, E. M., Sonbul, S. N., Almuhaini, E. A., & Al-Ghafari, A. B. (2025). Synergetic effect of doxorubicin and avenanthramide C on VDAC2/MTCH1 mitochondrial axis in breast cancer cells. International Journal of Health Sciences, 19(2), 26–41. Retrieved from https://pub.qu.edu.sa/index.php/journal/article/view/8828
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.


Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

    1. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.

  1. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
Copyright and license info is not available
Author biographies is not available.