Evaluation of The Efficacy of Resveratrol and Curcumin on The Expression of Bcl-2, Bax, and P53 Genes and GAFP Protein in Male Wistar Rats Model Glioblastoma Multiforme


  • Mostafa Rajabi Department of Basic Sciences, Faculty of Pharmacy and Pharmaceutical Science, Tehran Medical Science, Islamic Azad University, Tehran, Iran.
  • Tahereh Naji Department of Basic Sciences, Faculty of Pharmacy and Pharmaceutical Science, Tehran Medical Science, Islamic Azad University, Tehran, Iran.
  • Abdolreza Mohamadnia Chronic Respiratory Diseases Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran




Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor seen in humans. Several epidemiological studies have demonstrated the chemo-preventive function of naturally occurring food components in cancer. Polyphenolic compounds of natural origin possess promising therapeutic potential as drugs for the management of glioblastoma and are being explored as potential anticancer agents. Despite the promising benefits of natural polyphenolic compounds, their effectiveness in treating GBM is restricted by their limited bioavailability and permeability through the blood-brain barrier. Several compounds derived from plants have demonstrated potential as antitumor therapeutic agents by augmenting apoptosis-related pathways and causing cell cycle impairment in tumor cells, including those found in GBM cell lines. According to reports, curcumin exhibits noteworthy antitumor properties. The anti-glioblastoma effects of heterogeneous compounds can be attributed to their ability to upregulate apoptosis and autophagy, promote cell cycle arrest, interfere with tumor metabolism, and inhibit proliferation, neuroinflammation, chemoresistance, angiogenesis, and metastasis. The development of glioblastoma cancer cells was modestly inhibited by the combination of resveratrol and curcumin. We found that the combined treatments resveratrol with curcumin inhibit the Bcl-2 expression, the reduction of the expression of Bax and P53.The findings of this study offer substantiation that the administration of resveratrol with curcumin in combination may present a compelling alternative for combating GBM. Nevertheless, further clinical trials are necessary to validate the characteristics of these compounds both in vitro and in vivo.


Beylerli, O., et al., Therapeutic effect of natural polyphenols against glioblastoma. Front Cell Dev Biol, 2022. 10: p. 1036809.

Persano, F., G. Gigli, and S. Leporatti, Natural Compounds as Promising Adjuvant Agents in The Treatment of Gliomas. Int J Mol Sci, 2022. 23(6).

Alkahtani, S., et al., Cytotoxicity Mechanisms of Blue-Light-Activated Curcumin in T98G Cell Line: Inducing Apoptosis through ROS-Dependent Downregulation of MMP Pathways. International Journal of Molecular Sciences, 2023. 24(4): p. 3842.

Crespo, I., et al., Molecular and Genomic Alterations in Glioblastoma Multiforme. Am J Pathol, 2015. 185(7): p. 1820-33.

Farnebo, M., V.J. Bykov, and K.G. Wiman, The p53 tumor suppressor: a master regulator of diverse cellular processes and therapeutic target in cancer. Biochemical and biophysical research communications, 2010. 396(1): p. 85-89.

Álvarez-Guerrero, A.F. and R. López-Revilla, Biomarkers of gliomas and their impact on diagnosis, prognosis, and treatment. Revista mexicana de neurociencia, 2021. 22(1): p. 22-29.

Uceda-Castro, R., et al., GFAP splice variants fine-tune glioma cell invasion and tumour dynamics by modulating migration persistence. Scientific Reports, 2022. 12(1): p. 424.

Kotha, R.R. and D.L. Luthria, Curcumin: Biological, Pharmaceutical, Nutraceutical, and Analytical Aspects. Molecules, 2019. 24(16).

Koushki, M., et al., Resveratrol: A miraculous natural compound for diseases treatment. Food Sci Nutr, 2018. 6(8): p. 2473-2490.

Ko, J.H., et al., The Role of Resveratrol in Cancer Therapy. Int J Mol Sci, 2017. 18(12).

Zeng, L., et al., Advancements in nanoparticle-based treatment approaches for skin cancer therapy. Molecular Cancer, 2023. 22(1): p. 10.

Salehi, B., et al., Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines, 2018. 6(3).

Luo, S.-M., et al., The anti-cancer effect of four curcumin analogues on human glioma cells. OncoTargets and therapy, 2021. 14: p. 4345.

He, X., et al., Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling. Cancer Lett, 2011. 301(2): p. 168-76.

Zanotto-Filho, A., et al., Autophagy inhibition improves the efficacy of curcumin/temozolomide combination therapy in glioblastomas. 2015. 358(2): p. 220-231.

Jang, M., J.J.D.u.e. Pezzuto, and c. research, Cancer chemopreventive activity of resveratrol. 1999. 25(2-3): p. 65-77.

Singer, P., Animal liberation, in Animal Rights: The Changing Debate. 1975, Springer. p. 7-18.

Jamshidi, N., et al., The expression level of miRNA-601 in the serum of Iranian lung cancer patients and its association with smoking. 2023.

Jamshidi, N., M. Rajabi, and N.J.L.S.S.J. Jamshidi, Comparative investigation of miRNA422a serum expression level in healthy and metastatic lung cancer Patients by Real Time PCR method. 2023.

Biasibetti, E., et al., Comparison of Allogeneic and Syngeneic Rat Glioma Models by Using MRI and Histopathologic Evaluation. Comp Med, 2017. 67(2): p. 147-156.

Hanif, F., et al., Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment. Asian Pac J Cancer Prev, 2017. 18(1): p. 3-9.

Yang, J., et al., Effect of curcumin on Bcl-2 and Bax expression in nude mice prostate cancer. Int J Clin Exp Pathol, 2015. 8(8): p. 9272-8.

Wilken, R., et al., Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer, 2011. 10: p. 12.

Walker, B.C., S. Adhikari, and S. Mittal, Therapeutic Potential of Curcumin for the Treatment of Malignant Gliomas, in Gliomas, W. Debinski, Editor. 2021: Brisbane (AU).

Ryskalin, L., et al., The Multi-Faceted Effect of Curcumin in Glioblastoma from Rescuing Cell Clearance to Autophagy-Independent Effects. Molecules, 2020. 25(20).

Huang, T.-Y., et al., Curcuminoids suppress the growth and induce apoptosis through caspase-3-dependent pathways in glioblastoma multiforme (GBM) 8401 cells. Journal of agricultural and food chemistry, 2010. 58(19): p. 10639-10645.

Hol, E.M. and M. Pekny, Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. Current Opinion in Cell Biology, 2015. 32: p. 121-130.

Amalia, L., Glial Fibrillary Acidic Protein (GFAP): Neuroinflammation Biomarker in Acute Ischemic Stroke. J Inflamm Res, 2021. 14: p. 7501-7506.

Abdelhak, A., et al., Blood GFAP as an emerging biomarker in brain and spinal cord disorders. Nature Reviews Neurology, 2022. 18(3): p. 158-172.

Radu, R., et al., GFAPdelta: A Promising Biomarker and Therapeutic Target in Glioblastoma. Front Oncol, 2022. 12: p. 859247.

Shankar, S. and R.K. Srivastava, Involvement of Bcl-2 family members, phosphatidylinositol 3'-kinase/AKT and mitochondrial p53 in curcumin (diferulolylmethane)-induced apoptosis in prostate cancer. Int J Oncol, 2007. 30(4): p. 905-18.

Fu, H., et al., Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling. J Cell Physiol, 2018. 233(6): p. 4634-4642.

Hassan, F.U., et al., Curcumin as an Alternative Epigenetic Modulator: Mechanism of Action and Potential Effects. Front Genet, 2019. 10: p. 514.

Liu, Z., et al., Alisertib induces G(2)/M arrest, apoptosis, and autophagy via PI3K/Akt/mTOR- and p38 MAPK-mediated pathways in human glioblastoma cells. Am J Transl Res, 2017. 9(3): p. 845-873.

Li, Q.J., J.Q. Cai, and C.Y. Liu, Evolving Molecular Genetics of Glioblastoma. Chin Med J (Engl), 2016. 129(4): p. 464-71.

Lu, T.X., et al., TP53 dysfunction in diffuse large B-cell lymphoma. Crit Rev Oncol Hematol, 2016. 97: p. 47-55.

Haas-Kogan, D.A., et al., p53-Dependent G1 arrest and p53-independent apoptosis influence the radiobiologic response of glioblastoma. International Journal of Radiation Oncology*Biology*Physics, 1996. 36(1): p. 95-103.

Gjerset, R.A., et al., Use of wild-type p53 to achieve complete treatment sensitization of tumor cells expressing endogenous mutant p53. Mol Carcinog, 1995. 14(4): p. 275-85.

Mejia-Rodriguez, R., et al., Combined treatments with AZD5363, AZD8542, curcumin or resveratrol induce death of human glioblastoma cells by suppressing the PI3K/AKT and SHH signaling pathways. Biochem Biophys Rep, 2023. 33: p. 101430.

Mukherjee, S., et al., Liposomal TriCurin, a synergistic combination of curcumin, epicatechin gallate and resveratrol, repolarizes tumor-associated microglia/macrophages, and eliminates glioblastoma (GBM) and GBM stem cells. Molecules, 2018. 23(1): p. 201.

Liontas, A. and H. Yeger, Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma. Anticancer research, 2004. 24(2B): p. 987-998.




How to Cite

Rajabi, M., Naji, T. ., & Mohamadnia, . A. . (2023). Evaluation of The Efficacy of Resveratrol and Curcumin on The Expression of Bcl-2, Bax, and P53 Genes and GAFP Protein in Male Wistar Rats Model Glioblastoma Multiforme. The Journal of Applied Tissue Engineering, 9(1). https://doi.org/10.22034/JATE.2023.79



Original Articles