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Journals / Black Sea Journal of Engineering and Science / 2026 / Cilt: 9 Sayı: 4

Acute Modulation of PER2 Mrna Expression in Synchronized MCF-7 Breast Cancer Cells Following Honokiol Treatment: An 8-Hour Pilot Investigation

İlkay Civelek(NİĞDE ÖMER HALİSDEMİR ÜNİVERSİTESİ)0000-0002-8241-1596
Pages
1832–1837
Publication Date
2026-07-15
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AI Summary & Key Takeaways

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

However, these findings remain preliminary as they are based on a single 8-hour time point, necessitating future time-course and protein-level validations.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Honokiol has been reported to exert broad antineoplastic activity through multiple signaling pathways, while circadian gene dysregulation, including PER2 downregulation, is increasingly recognized in breast cancer.
📊
Key Findings & Data:In this pilot study, PER2 expression was examined to determine whether honokiol acutely modulates its levels in synchronized MCF-7 breast cancer cells after 8 h of treatment.
💡
Conclusion & Impact:However, these findings remain preliminary as they are based on a single 8-hour time point, necessitating future time-course and protein-level validations.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Honokiol · MCF-7 · Per2

Abstract

Honokiol has been reported to exert broad antineoplastic activity through multiple signaling pathways, while circadian gene dysregulation, including PER2 downregulation, is increasingly recognized in breast cancer. In this pilot study, PER2 expression was examined to determine whether honokiol acutely modulates its levels in synchronized MCF-7 breast cancer cells after 8 h of treatment. Cells were exposed to 5, 10, or 20 µM honokiol, with medium-only and DMSO vehicle controls included for comparison. PER2 mRNA levels were quantified by qRT-PCR and normalized to ACTB using the comparative Ct method. In this experiment, the DMSO vehicle group showed lower PER2 expression than the medium-only control, highlighting a vehicle-associated suppression under the present conditions. Interestingly, honokiol produced a non-linear, concentration-dependent response: treatment with 10 µM honokiol upregulated PER2 expression (~2.90-fold) compared to the DMSO vehicle, showing the strongest capacity to rescue the circadian clock suppression. In contrast, 5 µM and 20 µM doses showed expression levels closer to the DMSO baseline. These data suggest that acute honokiol exposure modulates PER2 expression in a concentration-sensitive manner, effectively rescuing solvent-induced chrono disruption. However, these findings remain preliminary as they are based on a single 8-hour time point, necessitating future time-course and protein-level validations.

Özet

Honokiol has been reported to exert broad antineoplastic activity through multiple signaling pathways, while circadian gene dysregulation, including PER2 downregulation, is increasingly recognized in breast cancer. In this pilot study, PER2 expression was examined to determine whether honokiol acutely modulates its levels in synchronized MCF-7 breast cancer cells after 8 h of treatment. Cells were exposed to 5, 10, or 20 µM honokiol, with medium-only and DMSO vehicle controls included for comparison. PER2 mRNA levels were quantified by qRT-PCR and normalized to ACTB using the comparative Ct method. In this experiment, the DMSO vehicle group showed lower PER2 expression than the medium-only control, highlighting a vehicle-associated suppression under the present conditions. Interestingly, honokiol produced a non-linear, concentration-dependent response: treatment with 10 µM honokiol upregulated PER2 expression (~2.90-fold) compared to the DMSO vehicle, showing the strongest capacity to rescue the circadian clock suppression. In contrast, 5 µM and 20 µM doses showed expression levels closer to the DMSO baseline. These data suggest that acute honokiol exposure modulates PER2 expression in a concentration-sensitive manner, effectively rescuing solvent-induced chrono disruption. However, these findings remain preliminary as they are based on a single 8-hour time point, necessitating future time-course and protein-level validations.

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Cite This Article

Civelek, İ. (2026). Acute Modulation of PER2 Mrna Expression in Synchronized MCF-7 Breast Cancer Cells Following Honokiol Treatment: An 8-Hour Pilot Investigation. Black Sea Journal of Engineering and Science, Cilt: 9 Sayı: 4, 1832–1837. https://doi.org/10.34248/bsengineering.1959923

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References (45)

  1. Amiama-Roig, A., Verdugo-Sivianes, E. M., Carnero, A., & Blanco, J. R. (2022). Chronotherapy: Circadian rhythms and their influence in cancer therapy. Cancers, 14(20), Article 5071. https://doi.org/10.3390/cancers14205071
  2. Avtanski, D. B., Nagalingam, A., Bonner, M. Y., Arbiser, J. L., Saxena, N. K., & Sharma, D. (2014). Honokiol inhibits epithelial-mesenchymal transition in breast cancer cells by targeting signal transducer and activator of transcription 3/Zeb1/E-cadherin axis. Molecular Oncology, 8(3), 565–580. https://doi.org/10.1016/j.molonc.2014.01.004
  3. Avtanski, D. B., Nagalingam, A., Bonner, M. Y., Arbiser, J. L., Saxena, N. K., & Sharma, D. (2015). Honokiol activates LKB1-miR-34a axis and antagonizes the oncogenic actions of leptin in breast cancer. Oncotarget, 6(30), 29947–29962. https://doi.org/10.18632/oncotarget.4937
  4. Baier, A., & Szyszka, R. (2020). Compounds from natural sources as protein kinase inhibitors. Biomolecules, 10(11), Article 1546. https://doi.org/10.3390/biom10111546
  5. Banik, K., Ranaware, A. M., Deshpande, V., Nalawade, S. P., Padmavathi, G., Bordoloi, D.,. & Kunnumakkara, A. B. (2019). Honokiol for cancer therapeutics: A traditional medicine that can modulate multiple oncogenic targets. Pharmacological Research, 144, 192–209. https://doi.org/10.1016/j.phrs.2019.04.004
  6. Broussard, J. L., Reynolds, A. C., Depner, C. M., Ferguson, S. A., Dawson, D., & Wright, K. P., Jr. (2017). Circadian rhythms versus daily patterns in human physiology and behavior. In V. Kumar (Ed.), Biological timekeeping: Clocks, rhythms and behaviour (pp. 279–295). Springer.
  7. Cadenas, C., Van De Sandt, L., Edlund, K., Lohr, M., Hellwig, B., Marchan, R.,. & Hengstler, J. G. (2014). Loss of circadian clock gene expression is associated with tumor progression in breast cancer. Cell Cycle, 13(20), 3282–3291. https://doi.org/10.4161/15384101.2014.954454
  8. Chen, J., Zhang, H., Qiu, M., Hu, J., Lin, L., Mai, L.,. & Zhao, H. (2025). Honokiol in the treatment of triple-negative breast cancer: A network pharmacology approach and experimental validation. Biochemical and Biophysical Research Communications, 771, Article 152008. https://doi.org/10.1016/j.bbrc.2025.152008
  9. Dai, X., Li, R. Z., Jiang, Z. B., Wei, C. L., Luo, L. X., Yao, X. J.,. & Leung, E. L. H. (2018). Honokiol inhibits proliferation, invasion and induces apoptosis through targeting lyn kinase in human lung adenocarcinoma cells. Frontiers in Pharmacology, 9, Article 558. https://doi.org/10.3389/fphar.2018.00558
  10. El-Tanani, M., Rabbani, S. A., Ali, A. A., Alfaouri, I. G. A., Al Nsairat, H., Al-Ani, I. H.,. & El-Tanani, Y. (2024). Circadian rhythms and cancer: Implications for timing in therapy. Discover Oncology, 15(1), Article 767. https://doi.org/10.1007/s12672-024-01643-4
  11. Golombek, D. A., & Rosenstein, R. E. (2010). Physiology of circadian entrainment. Physiological Reviews, 90(3), 1063–1102. https://doi.org/10.1152/physrev.00009.2009
  12. Hortobagyi, G. N., de la Garza Salazar, J., Pritchard, K., Amadori, D., Haidinger, R., Hudis, C. A.,. & ABREAST Investigators. (2005). The global breast cancer burden: Variations in epidemiology and survival. Clinical Breast Cancer, 6(5), 391–401. https://doi.org/10.3816/CBC.2005.n.043
  13. Hosseini, A., & Ghorbani, A. (2015). Cancer therapy with phytochemicals: Evidence from clinical studies. Avicenna Journal of Phytomedicine, 5(2), 84–97.
  14. Houghton, S. C., & Hankinson, S. E. (2021). Cancer progress and priorities: Breast cancer. Cancer Epidemiology, Biomarkers & Prevention, 30(5), 822–844.
  15. Huyen, P. V., Hien, N. T. T., Hanh, T. T. N., Duyen, N. H. H., Thuan, N. T. D., & Phan, N. H. T. (2025). Phytochemistry and biological activities of Magnolia genus: From 2003 to 2023. Phytochemistry Reviews, 24(6), 6311–6368.
  16. Kuo, S. J., Chen, S. T., Yeh, K. T., Hou, M. F., Chang, Y. S., Hsu, N. C., & Chang, J. G. (2009). Disturbance of circadian gene expression in breast cancer. Virchows Archiv, 454(4), 467–474. https://doi.org/10.1007/s00428-009-0761-7
  17. Lee, Y. J., Lee, Y. M., Lee, C. K., Jung, J. K., Han, S. B., & Hong, J. T. (2011). Therapeutic applications of compounds in the Magnolia family. Pharmacology & Therapeutics, 130(2), 157–176.
  18. Li, Z., Liu, Y., Zhao, X., Pan, X., Yin, R., Huang, C.,. & Wei, Y. (2008). Honokiol, a natural therapeutic candidate, induces apoptosis and inhibits angiogenesis of ovarian tumor cells. European Journal of Obstetrics & Gynecology and Reproductive Biology, 140(1), 95–102.
  19. Liu, H., Zang, C., Emde, A., Planas-Silva, M. D., Rosche, M., Kühnl, A.,. & Eucker, J. (2008). Anti-tumor effect of honokiol alone and in combination with other anti-cancer agents in breast cancer. European Journal of Pharmacology, 591(1–3), 43–51. https://doi.org/10.1016/j.ejphar.2008.06.026
  20. Luo, C., Li, N., Lu, B., Cai, J., Lu, M., Zhang, Y.,. & Dai, M. (2022). Global and regional trends in incidence and mortality of female breast cancer and associated factors at national level in 2000 to 2019. Chinese Medical Journal, 135(1), 42–51. https://doi.org/10.1097/CM9.0000000000001814
  21. Mayer, W. E., Maier, M., & Flach, D. (1985). Osmotica, dimethyl sulfoxide, parahydroxymercuribenzoate, and cyanide change the period of the circadian clock in the pulvini of Phaseolus coccineus L. Chronobiology International, 2(1), 11–17. https://doi.org/10.3109/07420528509055537
  22. Mikhaevich, E. I., Sorokin, D. V., & Scherbakov, A. M. (2023). Honokiol inhibits the growth of hormone-resistant breast cancer cells: Its promising effect in combination with metformin. Research in Pharmaceutical Sciences, 18(5), 580–591. https://doi.org/10.4103/1735-5362.383712
  23. Ong, C. P., Lee, W. L., Tang, Y. Q., & Yap, W. H. (2019). Honokiol: A review of its anticancer potential and mechanisms. Cancers, 12(1), Article 48. https://doi.org/10.3390/cancers12010048
  24. Reszka, E., & Przybek, M. (2016). Circadian genes in breast cancer. Advances in Clinical Chemistry, 75, 53–70. https://doi.org/10.1016/bs.acc.2016.03.005
  25. Ruan, W., Yuan, X., & Eltzschig, H. K. (2021). Circadian rhythm as a therapeutic target. Nature Reviews Drug Discovery, 20(4), 287–307. https://doi.org/10.1038/s41573-020-00109-w
  26. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660
  27. Verheijen, M., Lienhard, M., Schrooders, Y., Clayton, O., Nudischer, R., Boerno, S.,. & Caiment, F. (2019). DMSO induces drastic changes in human cellular processes and epigenetic landscape in vitro. Scientific Reports, 9(1), Article 4641. https://doi.org/10.1038/s41598-019-40660-0
  28. Vitaterna, M. H., Takahashi, J. S., & Turek, F. W. (2001). Overview of circadian rhythms. Alcohol Research & Health, 25(2), 85–88.
  29. Winter, W. L., Bosnoyan-Collins, L., Pinnaduwage, D., & Andrulis, I. L. (2007). Expression of the circadian clock genes Per1 and Per2 in sporadic and familial breast tumors. Neoplasia, 9(10), 797–800. https://doi.org/10.1593/neo.07595
  30. Wolf, I., O'Kelly, J., Wakimoto, N., Nguyen, A., Amblard, F., Karlan, B. Y.,. & Koeffler, H. P. (2007). Honokiol, a natural biphenyl, inhibits in vitro and in vivo growth of breast cancer through induction of apoptosis and cell cycle arrest. International Journal of Oncology, 30(6), 1529–1537. https://doi.org/10.3892/ijo.30.6.1529
  31. Xiang, S., Coffelt, S., Mao, L., Yuan, L., Cheng, Q., & Hill, S. (2008). Period-2: A tumor suppressor gene in breast cancer. Journal of Circadian Rhythms, 6, Article 4. https://doi.org/10.1186/1740-3391-6-4
  32. Xu, Y., Toh, K. L., Jones, C. R., Shin, J. Y., Fu, Y. H., & Ptáček, L. J. (2007). Modeling of a human circadian mutation yields insights into clock regulation by PER2. Cell, 128(1), 59–70. https://doi.org/10.1016/j.cell.2006.11.043
  33. Yang, X., Wood, P., Oh, E.-Y., Du-Quiton, J., Ansell, C. M., & Hrushesky, W. (2009). Down regulation of circadian clock gene Period 2 accelerates breast cancer growth by altering its daily growth rhythm. Breast Cancer Research and Treatment, 117(2), 423–431.
  34. Yi, X., Qi, M., Huang, M., Zhou, S., & Xiong, J. (2022). Honokiol inhibits HIF-1α-mediated glycolysis to halt breast cancer growth. Frontiers in Pharmacology, 13, Article 796763. https://doi.org/10.3389/fphar.2022.796763
  35. Banik, K., Ranaware, A. M., Deshpande, V., Nalawade, S. P., Padmavathi, G., Bordoloi, D.,. & Kunnumakkara, A. B. (2019). Honokiol for cancer therapeutics: A traditional medicine that can modulate multiple oncogenic targets. Pharmacological Research, 144, 192–209. https://doi.org/10.1016/j.phrs.2019.04.004
  36. Cadenas, C., Van De Sandt, L., Edlund, K., Lohr, M., Hellwig, B., Marchan, R.,. & Hengstler, J. G. (2014). Loss of circadian clock gene expression is associated with tumor progression in breast cancer. Cell Cycle, 13(20), 3282–3291. https://doi.org/10.4161/15384101.2014.954454
  37. Chen, J., Zhang, H., Qiu, M., Hu, J., Lin, L., Mai, L.,. & Zhao, H. (2025). Honokiol in the treatment of triple-negative breast cancer: A network pharmacology approach and experimental validation. Biochemical and Biophysical Research Communications, 771, Article 152008. https://doi.org/10.1016/j.bbrc.2025.152008
  38. Dai, X., Li, R. Z., Jiang, Z. B., Wei, C. L., Luo, L. X., Yao, X. J.,. & Leung, E. L. H. (2018). Honokiol inhibits proliferation, invasion and induces apoptosis through targeting lyn kinase in human lung adenocarcinoma cells. Frontiers in Pharmacology, 9, Article 558. https://doi.org/10.3389/fphar.2018.00558
  39. El-Tanani, M., Rabbani, S. A., Ali, A. A., Alfaouri, I. G. A., Al Nsairat, H., Al-Ani, I. H.,. & El-Tanani, Y. (2024). Circadian rhythms and cancer: Implications for timing in therapy. Discover Oncology, 15(1), Article 767. https://doi.org/10.1007/s12672-024-01643-4
  40. Hortobagyi, G. N., de la Garza Salazar, J., Pritchard, K., Amadori, D., Haidinger, R., Hudis, C. A.,. & ABREAST Investigators. (2005). The global breast cancer burden: Variations in epidemiology and survival. Clinical Breast Cancer, 6(5), 391–401. https://doi.org/10.3816/CBC.2005.n.043
  41. Li, Z., Liu, Y., Zhao, X., Pan, X., Yin, R., Huang, C.,. & Wei, Y. (2008). Honokiol, a natural therapeutic candidate, induces apoptosis and inhibits angiogenesis of ovarian tumor cells. European Journal of Obstetrics & Gynecology and Reproductive Biology, 140(1), 95–102.
  42. Liu, H., Zang, C., Emde, A., Planas-Silva, M. D., Rosche, M., Kühnl, A.,. & Eucker, J. (2008). Anti-tumor effect of honokiol alone and in combination with other anti-cancer agents in breast cancer. European Journal of Pharmacology, 591(1–3), 43–51. https://doi.org/10.1016/j.ejphar.2008.06.026
  43. Luo, C., Li, N., Lu, B., Cai, J., Lu, M., Zhang, Y.,. & Dai, M. (2022). Global and regional trends in incidence and mortality of female breast cancer and associated factors at national level in 2000 to 2019. Chinese Medical Journal, 135(1), 42–51. https://doi.org/10.1097/CM9.0000000000001814
  44. Verheijen, M., Lienhard, M., Schrooders, Y., Clayton, O., Nudischer, R., Boerno, S.,. & Caiment, F. (2019). DMSO induces drastic changes in human cellular processes and epigenetic landscape in vitro. Scientific Reports, 9(1), Article 4641. https://doi.org/10.1038/s41598-019-40660-0
  45. Wolf, I., O'Kelly, J., Wakimoto, N., Nguyen, A., Amblard, F., Karlan, B. Y.,. & Koeffler, H. P. (2007). Honokiol, a natural biphenyl, inhibits in vitro and in vivo growth of breast cancer through induction of apoptosis and cell cycle arrest. International Journal of Oncology, 30(6), 1529–1537. https://doi.org/10.3892/ijo.30.6.1529