Combined Anticancer Effects of Curcumin and Serotonin on U87 Human Glioblastoma Cells: In Vitro and Molecular Docking Analysis

Yasemin Yılmazer

doi:10.17776/csj.1914549

Combined Anticancer Effects of Curcumin and Serotonin on U87 Human Glioblastoma Cells: In Vitro and Molecular Docking Analysis

Abstract

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and is characterized by rapid proliferation, extensive invasion, and resistance to conventional therapies. Natural bioactive compounds have attracted increasing attention as potential anticancer agents due to their multi-targeted mechanisms and relatively low toxicity. In this study, the antiproliferative and antimigratory effects of curcumin and serotonin, individually and in combination, were investigated in U87 human glioblastoma cells. Cell viability was evaluated using the MTS assay after treatment with different concentrations of curcumin and serotonin for 24–96 h. A scratch wound healing assay was performed to assess their effects on cell migration. In addition, molecular docking analyses were conducted to investigate the interactions of curcumin and serotonin with cancer-related proteins, including BCL-2, PI3K, and mTOR. The results demonstrated that both curcumin (20,30 and 40 μM) and serotonin (200 μM) reduced cell viability in a dose- and time-dependent manner. Their combined treatment produced a stronger inhibitory effect on cell proliferation and migration compared with individual treatments. Molecular docking analysis also revealed stronger binding affinities for the combined ligands toward PI3K, mTOR, and BCL-2. These findings suggest that the combination of curcumin and serotonin may represent a promising multi-targeted therapeutic strategy for glioblastoma.

Keywords

Anticancer, Curcumin, Glioblastoma, Molecular Docking, Serotonin

Ethical Statement

The author declares that no ethics committee approval or special legal permission was required for the materials and methods used in this study.

Thanks

The human glioma U87 cell line was a kind gift of Assoc. Prof. Dr Zeynep Büşra Bolat at University of Health Sciences.

References

Afshari, A. R., Sanati, M., Aminyavari, S., Shakeri, F., Bibak, B., Keshavarzi, Z., Soukhtanloo, M., Jalili-Nik, M., Sadeghi, M. M., Mollazadeh, H., Johnston, T. P., & Sahebkar, A. (2022). Advantages and drawbacks of dexamethasone in glioblastoma multiforme. Critical reviews in oncology/hematology, 172, 103625. https://doi.org/10.1016/j.critrevonc.2022.103625
Grech, N., Dalli, T., Mizzi, S., Meilak, L., Calleja, N., & Zrinzo, A. (2020). Rising Incidence of Glioblastoma Multiforme in a Well-Defined Population. Cureus, 12(5), e8195. https://doi.org/10.7759/cureus.8195
Davis M. E. (2016). Glioblastoma: Overview of Disease and Treatment. Clinical journal of oncology nursing, 20(5 Suppl), S2–S8. https://doi.org/10.1188/16.CJON.S1.2-8
Yang, S., Xie, C., Guo, T., Li, H., Li, N., Zhou, S., Wang, X., & Xie, C. (2022). Simvastatin Inhibits Tumor Growth and Migration by Mediating Caspase-1-Dependent Pyroptosis in Glioblastoma Multiforme. World neurosurgery, 165, e12–e21. https://doi.org/10.1016/j.wneu.2022.03.089
Afshari, A. R., Motamed-Sanaye, A., Sabri, H., Soltani, A., Karkon-Shayan, S., Radvar, S., Javid, H., Mollazadeh, H., Sathyapalan, T., & Sahebkar, A. (2021). Neurokinin-1 Receptor (NK-1R) Antagonists: Potential Targets in the Treatment of Glioblastoma Multiforme. Current medicinal chemistry, 28(24), 4877–4892. https://doi.org/10.2174/0929867328666210113165805
Jalili-Nik, M., Afshari, A. R., Sabri, H., Bibak, B., Mollazadeh, H., & Sahebkar, A. (2021). Zerumbone, a ginger sesquiterpene, inhibits migration, invasion, and metastatic behavior of human malignant glioblastoma multiforme in vitro. BioFactors (Oxford, England), 47(5), 729–739. https://doi.org/10.1002/biof.1756
Ye, J., Zhang, R., Wu, F., Zhai, L., Wang, K., Xiao, M., Xie, T., & Sui, X. (2018). Non-apoptotic cell death in malignant tumor cells and natural compounds. Cancer letters, 420, 210–227. https://doi.org/10.1016/j.canlet.2018.01.061
Yuan, H., Ma, Q., Ye, L., & Piao, G. (2016). The Traditional Medicine and Modern Medicine from Natural Products. Molecules (Basel, Switzerland), 21(5), 559. https://doi.org/10.3390/molecules21050559
Kunnumakkara, A. B., Bordoloi, D., Padmavathi, G., Monisha, J., Roy, N. K., Prasad, S., & Aggarwal, B. B. (2017). Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. British journal of pharmacology, 174(11), 1325–1348. https://doi.org/10.1111/bph.13621
Nelson, K. M., Dahlin, J. L., Bisson, J., Graham, J., Pauli, G. F., & Walters, M. A. (2017). The Essential Medicinal Chemistry of Curcumin. Journal of medicinal chemistry, 60(5), 1620–1637. https://doi.org/10.1021/acs.jmedchem.6b00975

Ravindran, J., Prasad, S., & Aggarwal, B. B. (2009). Curcumin and cancer cells: how many ways can curry kill tumor cells selectively?. The AAPS journal, 11(3), 495–510. https://doi.org/10.1208/s12248-009-9128-x
Hewlings, S. J., & Kalman, D. S. (2017). Curcumin: A Review of Its Effects on Human Health. Foods (Basel, Switzerland), 6(10), 92. https://doi.org/10.3390/foods6100092
Gao, X., Deeb, D., Jiang, H., Liu, Y. B., Dulchavsky, S. A., & Gautam, S. C. (2005). Curcumin differentially sensitizes malignant glioma cells to TRAIL/Apo2L-mediated apoptosis through activation of procaspases and release of cytochrome c from mitochondria. Journal of experimental therapeutics & oncology, 5(1), 39–48.
Kim, S. Y., Jung, S. H., & Kim, H. S. (2005). Curcumin is a potent broad spectrum inhibitor of matrix metalloproteinase gene expression in human astroglioma cells. Biochemical and biophysical research communications, 337(2), 510–516. https://doi.org/10.1016/j.bbrc.2005.09.079
Nagai, S., Kurimoto, M., Washiyama, K., Hirashima, Y., Kumanishi, T., & Endo, S. (2005). Inhibition of cellular proliferation and induction of apoptosis by curcumin in human malignant astrocytoma cell lines. Journal of neuro-oncology, 74(2), 105–111. https://doi.org/10.1007/s11060-004-5757-1
Woo, M. S., Jung, S. H., Kim, S. Y., Hyun, J. W., Ko, K. H., Kim, W. K., & Kim, H. S. (2005). Curcumin suppresses phorbol ester-induced matrix metalloproteinase-9 expression by inhibiting the PKC to MAPK signaling pathways in human astroglioma cells. Biochemical and biophysical research communications, 335(4), 1017–1025. https://doi.org/10.1016/j.bbrc.2005.07.174
Belkaid, A., Copland, I. B., Massillon, D., & Annabi, B. (2006). Silencing of the human microsomal glucose-6-phosphate translocase induces glioma cell death: potential new anticancer target for curcumin. FEBS letters, 580(15), 3746–3752. https://doi.org/10.1016/j.febslet.2006.05.071
Patil, V. M., Das, S., & Balasubramanian, K. (2016). Quantum Chemical and Docking Insights into Bioavailability Enhancement of Curcumin by Piperine in Pepper. The journal of physical chemistry. A, 120(20), 3643–3653. https://doi.org/10.1021/acs.jpca.6b01434
Schneider, M. A., Heeb, L., Beffinger, M. M., Pantelyushin, S., Linecker, M., Roth, L., Lehmann, K., Ungethüm, U., Kobold, S., Graf, R., van den Broek, M., Vom Berg, J., Gupta, A., & Clavien, P. A. (2021). Attenuation of peripheral serotonin inhibits tumor growth and enhances immune checkpoint blockade therapy in murine tumor models. Science translational medicine, 13(611), eabc8188. https://doi.org/10.1126/scitranslmed.abc8188
Rieder, M., Gauchel, N., Bode, C., & Duerschmied, D. (2021). Serotonin: a platelet hormone modulating cardiovascular disease. Journal of thrombosis and thrombolysis, 52(1), 42–47. https://doi.org/10.1007/s11239-020-02331-0
Balakrishna, P., George, S., Hatoum, H., & Mukherjee, S. (2021). Serotonin pathway in cancer. International Journal of Molecular Sciences, 22(3), 1268. https://doi.org/10.3390/ijms22031268
Karmakar S, Lal G. Role of serotonin receptor signaling in cancer cells and anti-tumor immunity. Theranostics. 2021 Mar 11;11(11):5296-5312. doi: 10.7150/thno.55986. PMID: 33859748; PMCID: PMC8039959.
Zhang, H., Liu, Z., Cheng, J., Jiang, Y., Zheng, X., Zhang, C., & Li, Y. (2025). HTR1D regulates the PI3K/Akt signaling pathway to impact glioblastoma development and resistance to temozolomide. Chemico-biological interactions, 421, 111748. https://doi.org/10.1016/j.cbi.2025.111748
Zhang, H. Q., Zhang, D. M., Huang, Z. Z., Cheng, J., Zhang, C., Lin, N. M., & Li, Y. (2025). Vortioxetine exhibits anti-glioblastoma activity via the PI3K-Akt signaling pathway. Iranian journal of basic medical sciences, 28(4), 401–408. https://doi.org/10.22038/ijbms.2025.82513.17836
Liang, CC., Park, A. & Guan, JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc 2, 329–333 (2007). https://doi.org/10.1038/nprot.2007.30
Kim, S., Thiessen, P. A., Bolton, E. E., Chen, J., Fu, G., Gindulyte, A., Han, L., He, J., He, S., Shoemaker, B. A., Wang, J., Yu, B., Zhang, J., & Bryant, S. H. (2016). PubChem Substance and Compound databases. Nucleic Acids Research, 44(Database issue), D1202. https://doi.org/10.1093/NAR/GKV951
Eberhardt, J., Santos-Martins, D., Tillack, A. F., & Forli, S. (2021). AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings. Journal of Chemical Information and Modeling, 61(8), 3891–3898. https://doi.org/10.1021/ACS.JCIM.1C00203/SUPPL_FILE/CI1C00203_SI_002.ZIP
Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/JCC.21334
Meng, E. C., Goddard, T. D., Pettersen, E. F., Couch, G. S., Pearson, Z. J., Morris, J. H., & Ferrin, T. E. (2023). UCSF ChimeraX: Tools for structure building and analysis. Protein Science, 32(11), e4792. https://doi.org/10.1002/pro.4792
Wang, Z., Liu, F., Liao, W., Yu, L., Hu, Z., Li, M., & Xia, H. (2020). Curcumin suppresses glioblastoma cell proliferation by p-AKT/mTOR pathway and increases the PTEN expression. Archives of biochemistry and biophysics, 689, 108412. https://doi.org/10.1016/j.abb.2020.108412
Maiti, P., Scott, J., Sengupta, D., Al-Gharaibeh, A., & Dunbar, G. L. (2019). Curcumin and Solid Lipid Curcumin Particles Induce Autophagy, but Inhibit Mitophagy and the PI3K-Akt/mTOR Pathway in Cultured Glioblastoma Cells. International journal of molecular sciences, 20(2), 399. https://doi.org/10.3390/ijms20020399
Akkoç, Y., Berrak, Ö., Arısan, E. D., Obakan, P., Çoker-Gürkan, A., & Palavan-Ünsal, N. (2015). Inhibition of PI3K signaling triggered apoptotic potential of curcumin which is hindered by Bcl-2 through activation of autophagy in MCF-7 cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 71, 161–171. https://doi.org/10.1016/j.biopha.2015.02.029
Yin, X., Wang, J., Ge, M., Feng, X., & Zhang, G. (2024). Designing Small Molecule PI3Kγ Inhibitors: A Review of Structure-Based Methods and Computational Approaches. Journal of Medicinal Chemistry, 67(13), 10530–10547. https://doi.org/10.1021/acs.jmedchem.4c00347

Details

Primary Language

English

Subjects

Cancer Biology

Journal Section

Research Article

Authors

Yasemin Yılmazer ^*
0000-0003-2190-073X
Türkiye

Publication Date

October 27, 2026

Submission Date

March 23, 2026

Acceptance Date

September 17, 2026

Published in Issue

Year 2026 Volume: 47 Number: 5

DOI

https://doi.org/10.17776/csj.1914549

IZ

https://izlik.org/JA68GE75CE

APA

Yılmazer, Y. (2026). Combined Anticancer Effects of Curcumin and Serotonin on U87 Human Glioblastoma Cells: In Vitro and Molecular Docking Analysis. Cumhuriyet Science Journal, 47(5), 884-891. https://doi.org/10.17776/csj.1914549

AMA

1.Yılmazer Y. Combined Anticancer Effects of Curcumin and Serotonin on U87 Human Glioblastoma Cells: In Vitro and Molecular Docking Analysis. CSJ. 2026;47(5):884-891. doi:10.17776/csj.1914549

Chicago

Yılmazer, Yasemin. 2026. “Combined Anticancer Effects of Curcumin and Serotonin on U87 Human Glioblastoma Cells: In Vitro and Molecular Docking Analysis”. Cumhuriyet Science Journal 47 (5): 884-91. https://doi.org/10.17776/csj.1914549.

EndNote

Yılmazer Y (October 1, 2026) Combined Anticancer Effects of Curcumin and Serotonin on U87 Human Glioblastoma Cells: In Vitro and Molecular Docking Analysis. Cumhuriyet Science Journal 47 5 884–891.

IEEE

[1]Y. Yılmazer, “Combined Anticancer Effects of Curcumin and Serotonin on U87 Human Glioblastoma Cells: In Vitro and Molecular Docking Analysis”, CSJ, vol. 47, no. 5, pp. 884–891, Oct. 2026, doi: 10.17776/csj.1914549.

ISNAD

Yılmazer, Yasemin. “Combined Anticancer Effects of Curcumin and Serotonin on U87 Human Glioblastoma Cells: In Vitro and Molecular Docking Analysis”. Cumhuriyet Science Journal 47/5 (October 1, 2026): 884-891. https://doi.org/10.17776/csj.1914549.

JAMA

1.Yılmazer Y. Combined Anticancer Effects of Curcumin and Serotonin on U87 Human Glioblastoma Cells: In Vitro and Molecular Docking Analysis. CSJ. 2026;47:884–891.

MLA

Yılmazer, Yasemin. “Combined Anticancer Effects of Curcumin and Serotonin on U87 Human Glioblastoma Cells: In Vitro and Molecular Docking Analysis”. Cumhuriyet Science Journal, vol. 47, no. 5, Oct. 2026, pp. 884-91, doi:10.17776/csj.1914549.

Vancouver

1.Yasemin Yılmazer. Combined Anticancer Effects of Curcumin and Serotonin on U87 Human Glioblastoma Cells: In Vitro and Molecular Docking Analysis. CSJ. 2026 Oct. 1;47(5):884-91. doi:10.17776/csj.1914549

As of 2026, Cumhuriyet Science Journal will be published in six issues per year, released in February, April, June, August, October, and December

Combined Anticancer Effects of Curcumin and Serotonin on U87 Human Glioblastoma Cells: In Vitro and Molecular Docking Analysis

Abstract

Keywords

Ethical Statement

Thanks

References

Details

Primary Language

Subjects

Journal Section

Authors

Publication Date

Submission Date

Acceptance Date

Published in Issue

DOI

IZ

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