Journals / Experimed / 2026 / Volume: 16 Issue: 1

Transcriptomic Profiling Reveals Cell Cycle and DNA Repair Pathway Modulation in Triple-Negative Breast Cancer Cells Exposed to Polyphenol-rich Propolis

Mehmet Fatih Seyhan(ISTANBUL YENI YUZYIL UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS)0000-0002-6218-0049
Özlem Timirci Kahraman(ISTANBUL UNIVERSITY, AZIZ SANCAR INSTITUTE OF EXPERIMENTAL MEDICINE, DEPARTMENT OF MOLECULAR MEDICINE)0000-0002-2641-5613
Naci Şenkal(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE)0000-0001-7072-8724
Halil Ibrahim Kisakesen(ISTANBUL TECHNICAL UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS, DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS)0000-0002-0351-4205
Allison Pınar Eronat(HALIC UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS, MOLECULAR BIOLOGY AND GENETICS PR. (PAID))0000-0002-8095-1759
Tülin Öztürk(ISTANBUL UNIVERSITY-CERRAHPASA, CERRAHPAŞA SCHOOL OF MEDICINE, DEPARTMENT OF SURGICAL MEDICAL SCIENCES, DEPARTMENT OF MEDICAL PATHOLOGY)0000-0001-6910-1131
Fatih Yanar(BOGAZICI UNIVERSITY, FACULTY OF ARTS AND SCIENCES, DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS, MOLECULAR BIOLOGY AND GENETICS PR. (ENGLISH))0000-0003-1399-3382
Hülya Yılmaz Aydoğan(ISTANBUL UNIVERSITY, AZIZ SANCAR INSTITUTE OF EXPERIMENTAL MEDICINE, DEPARTMENT OF MOLECULAR MEDICINE)0000-0002-8837-6664
Oğuz Öztürk(ISTANBUL UNIVERSITY, AZIZ SANCAR INSTITUTE OF EXPERIMENTAL MEDICINE, DEPARTMENT OF MOLECULAR MEDICINE)0000-0002-2439-9269
Journal
Experimed
Pages
—
Publication Date
2026-08-27
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Conclusion: The findings of the microarray assay have highlighted that propolis from Türkiye has the capacity to inhibit the cell division process at many points and modulate the DNA repair mechanism.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Objective: Triple-negative breast cancer (TNBC) is the most invasive subtype of breast cancer distinguished by its high recurrence rates and clinical aggression.
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Key Findings & Data:Materials and Methods: This study aimed to evaluate the effects of 50 µg/mL propolis concentration for 48 and 72hours on gene expression levels in MDA-MB-231 cells using microarray assay.
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Conclusion & Impact:Conclusion: The findings of the microarray assay have highlighted that propolis from Türkiye has the capacity to inhibit the cell division process at many points and modulate the DNA repair mechanism.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:triple negative breast cancer · propolis · MDA-MB-231

Abstract

Objective: Triple-negative breast cancer (TNBC) is the most invasive subtype of breast cancer distinguished by its high recurrence rates and clinical aggression. Honey bees naturally create propolis, which can be used as an alternative therapy for breast cancer due to its anti-cancer properties. The study aimed to examine the impacts of propolis by elucidating potential anticarcinogenic and modulatory effects focusing on whole-genome expression levels. Materials and Methods: This study aimed to evaluate the effects of 50 µg/mL propolis concentration for 48 and 72hours on gene expression levels in MDA-MB-231 cells using microarray assay. Microarray results were also validated using selected genes such as BIRC5, CDC25C, CCN1, CCN2, and CDK1 via the quantitative reverse transcription polymerase chain reaction (qRT-PCR) method. Results: According to bioinformatics analysis, 315 gene expression changed statistically significantly following 50 µg/ mL propolis treatment at all-time intervals. GeneSpring pathway analysis revealed significant effects of propolis on pathways related to cell division, including cell cycle and Rb in cancer. Propolis led to downregulation of CDK1, a gene associated with the cell cycle, and expression of genes associated with DNA repair mechanisms, including BRCA1, BARD1, RAD51, and CHEK1. Conclusion: The findings of the microarray assay have highlighted that propolis from Türkiye has the capacity to inhibit the cell division process at many points and modulate the DNA repair mechanism.

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Cite This Article

Seyhan, M. F., Kahraman, Ö. T., Şenkal, N., Kisakesen, H. I., Eronat, A. P., Öztürk, T., Yanar, F., Aydoğan, H. Y., Öztürk, O. (2026). Transcriptomic Profiling Reveals Cell Cycle and DNA Repair Pathway Modulation in Triple-Negative Breast Cancer Cells Exposed to Polyphenol-rich Propolis. Experimed, Volume: 16 Issue: 1. https://doi.org/10.26650/experimed.1823647

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References (32)

  1. Wilkinson L, Gathani T. Understanding breast cancer as a global health concern. Br J Radiol 2022; 95(1130): 20211033. google scholar
  2. Obidiro O, Battogtokh G, Akala EO. Triple negative breast cancer treatment options and limitations: future outlook. Pharmaceutics 2023; 15(7): 1796. google scholar
  3. Zagami P, Carey LA. Triple negative breast cancer: Pitfalls and progress. NPJ Breast Cancer 2022; 8(1): 95. google scholar
  4. Vagia E, Mahalingam D, Cristofanilli M. The landscape of targeted therapies in TNBC. Cancers 2020; 12(4): 916. google scholar
  5. Keihan Shokooh M, Emami F, Jeong JH, Yook S. Bio-inspired and smart nanoparticles for triple negative breast cancer microenvironment. Pharmaceutics 2021;13(2): 287. google scholar
  6. Simone-Finstrom M, Spivak M. Propolis and bee health: The natural history and significance of resin use by honey bees. Apidologie 2010; 41(3): 295-311. google scholar
  7. Stojanović S, Najman SJ, Bogdanova-Popov B, Najman SS. Propolis: chemical composition, biological and pharmacological activity-A review. Acta Med Medianae 2020; 59(2): 108-13. google scholar
  8. Anjum SI, Ullah A, Khan KA, Attaullah M, Khan H, Ali H, et al. Composition and functional properties of propolis (bee glue): A review. Saudi J Biol Sci 2019; 26(7): 1695-703. google scholar
  9. Oršolić N, Jazvinšćak Jembrek M. Molecular and cellular mechanisms of propolis and its polyphenolic compounds against cancer. Int J Mol Sci 2022; 23(18): 10479. google scholar
  10. Valivand N, Aravand S, Lotfi H, Esfahani AJ, Ahmadpour-Yazdi H, Gheibi N. Propolis: a natural compound with potential as an adjuvant in cancer therapy – a review of signaling pathways. Mol Biol Rep 2024; 51(1): 931. google scholar
  11. Seyhan MF, Yılmaz E, Timirci-Kahraman Ö, Saygılı N, Kısakesen Hİ, Gazioğlu S, et al. Different propolis samples, phenolic content, and breast cancer cell lines: Variable cytotoxicity ranging from ineffective to potent. IUBMB Life 2019; 71(5): 619-31. google scholar
  12. do Nascimento RG, Otoni KM. Histological and molecular classification of breast cancer. Mastology 2020; 30: e20200024. google scholar
  13. Dewi C, Fristiohady A, Amalia R, Khairul Ikram NK, Ibrahim S, Muchtaridi M. Signaling pathways and natural compounds in triple-negative breast cancer cell line. Molecules 2022; 27(12): 3661. google scholar
  14. Wang DY, Jiang Z, Ben-David Y, Woodgett JR, Zacksenhaus E. Molecular stratification within triple-negative breast cancer subtypes. Sci Rep 2019; 9(1): 19107. google scholar
  15. Popova M, Giannopoulou E, Skalicka-Woźniak K, Graikou K, Widelski J, Bankova V, et al. Characterization and biological evaluation of propolis from Poland. Molecules 2017; 22(7): 1159. google scholar
  16. Noureddine H, Hage-Sleiman R, Wehbi B, Fayyad-Kazan H, Hayar S, Traboulssi M, et al. Chemical characterization and cytotoxic activity evaluation of Lebanese propolis. Biomed Pharmacother 2017; 95: 298-307. google scholar
  17. Jung BI, Kim MS, Kim HA, Kim D, Yang J, Her S, et al. Caffeic acid phenethyl ester, a component of beehive propolis, is a novel selective estrogen receptor modulator. Phytother Res 2010; 24(2): 295-300. google scholar
  18. Vatansever SH, Sorkun K, Ismet Deliloğlu Gurhan S, Ozdal-Kurt F, Turkoz E, Gencay O, et al. Propolis from Turkey induces apoptosis through activating caspases in human breast carcinoma cell lines. Acta Histochem 2010;112(6): 546-56. google scholar
  19. Ishihara M, Naoi K, Hashita M, Itoh Y, Suzui M. Growth inhibitory activity of ethanol extracts of Chinese and Brazilian propolis in four human colon carcinoma cell lines. Oncol Rep 2009; 22(2): 349-54. google scholar
  20. Li F, Awale S, Tezuka Y, Kadota S. Cytotoxicity of constituents from Mexican propolis against a panel of six different cancer cell lines. Nat Prod Commun 2010; 5(10):1601-06. google scholar
  21. Amalia E, Diantini A, Subarnas A. Water-soluble propolis and bee pollen of Trigona spp. from South Sulawesi Indonesia induce apoptosis in the human breast cancer MCF-7 cell line. Oncol Lett 2020; 20(5): 274. google scholar
  22. Farghadani R, Naidu R. The anticancer mechanism of action of selected polyphenols in triple-negative breast cancer (TNBC). Biomed Pharmacother. 2023; 165: 115170. google scholar
  23. de Freitas Meirelles LE, de Assis Carvalho ARB, Ferreira Damke GMZ, Souza RP, Damke E, de Souza Bonfim-Mendonça P, et al. Antitumoral potential of Artepillin C, a compound derived from Brazilian propolis, against breast cancer cell lines. Anticancer Agents Med Chem 2024; 24(2): 117-24. google scholar
  24. Melekoglu A, Ceviz AB, Eronat AP, Ozturk T, Pehlivan F, Yılmaz-Aydogan H, et al. Synergistic and dose-dependent effects of pinostrobin, pinocembrin and pinobanksin on different breast cancer cell lines. Kafkas Univ Vet Fak Derg 2024; 30 (1): 23-30. google scholar
  25. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nature Reviews Cancer 2009; 9(3): 153- 66. google scholar
  26. Zhao Y, Wang Y, Zhu F, Zhang J, Ma X, Zhang D. Gene expression profiling revealed MCM3 to be a better marker than Ki67 in prognosis of invasive ductal breast carcinoma patients. Clin Exp Med 2020; 20(2): 249-59. google scholar
  27. Seyhan MF, Timirci-Kahraman Ö, Eronat AP, Yılmaz E, Ceviz AB, Kisakesen HI, et al. Whole genome expression analysis identifies multiple targeted integrative effects of polyphenol-rich propolis on HER-2-positive breast cancer cell line. Rec Nat Prod 2024; 18(2): 201-11. google scholar
  28. Seyhan MF, Eronat AP, Diren A, Tuzuner MB, Ceviz AB, Yilmaz-Aydogan H, et al. A mixture of potent polyphenolic anticarcinogens: Microarray analysis of their efficacy in MCF-7 and MCF-10A cell lines. Rec Nat Prod 2026; 20(4): e25103658. google scholar
  29. Tufail, M. DNA repair pathways in breast cancer: from mechanisms to clinical applications. Breast Cancer Res Treat 2023; 200(3): 305-21. google scholar
  30. Woditschka S, Evans L, Duchnowska R, Reed LT, Palmieri D, Qian Y, et al. DNA doublestrand break repair genes and oxidative damage in brain metastasis of breast cancer. J Natl Cancer Inst 2014; 106(7): dju145. google scholar
  31. Shi Z, Kuai M, Li B, Akowuah CF, Wang Z, Pan Y, Tang M, Yang X, Lü P. The role of VEGF in cancer angiogenesis and tumorigenesis: Insights for anti-VEGF therapy. Cytokine 2025; 189: 156908. google scholar
  32. Liu X, Zhang J, Yi T, Li H, Tang X, Liu D, Wu D, Li Y. Decoding tumor angiogenesis: pathways, mechanisms, and future directions in anti-cancer strategies. Biomark Res 2025; 13(1): 62. google scholar