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

IF 2 Q2 MEDICINE, GENERAL & INTERNAL International Journal of Health Sciences-IJHS Pub Date : 2025-03-01

Ehab M M Ali, Sultan N Sonbul, Eman A Almuhaini, Ayat B Al-Ghafari

{"title":"Synergetic effect of doxorubicin and avenanthramide C on VDAC2/MTCH1 mitochondrial axis in breast cancer cells.","authors":"Ehab M M Ali, Sultan N Sonbul, Eman A Almuhaini, Ayat B Al-Ghafari","doi":"","DOIUrl":null,"url":null,"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.","PeriodicalId":47093,"journal":{"name":"International Journal of Health Sciences-IJHS","volume":"19 2","pages":"26-41"},"PeriodicalIF":2.0000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877058/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Health Sciences-IJHS","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}

引用次数: 0

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.