Understanding How Madecassic Acid Affects Glioblastoma Cells: Its Antioxidant and Anti-cancer Properties

Year 2023, Volume: 1 Issue: 2, 63 - 71, 29.08.2023

Ufuk Okkay , Irmak Ferah Okkay , Fatma Yesilyurt , Selcuk Senyayla

Abstract

Glioblastoma, a malignant brain tumor, poses significant therapeutic challenges due to its aggressive nature and limited treatment options. The search for novel compounds with potential therapeutic efficacy against this devastating disease remains imperative. Madecassic acid (MA), a triterpenoid derived from Centella asiatica, has emerged as a promising candidate with multifaceted pharmacological activities, including antioxidant and antitumor effects. However, its specific impact on glioblastoma cells necessitates further exploration to fully comprehend its therapeutic potential. In this investigation, we examined the effects of MA on a human glioblastoma cell line, with a primary focus on its antioxidant and anti-proliferative properties. Utilizing a comprehensive range of cellular and molecular assays, we unraveled the potential of MA in scavenging free radicals, mitigating oxidative stress, and inhibiting glioblastoma cell proliferation. The study revealed that MA significantly inhibited glioblastoma cell growth. Furthermore, MA-treated cells exhibited higher antioxidant enzyme activity and lower oxidative stress levels compared to untreated cells. These findings demonstrate the potential of MA as an effective therapeutic agent against glioblastoma. By elucidating its antioxidant and anti-proliferative effects, this research opens new avenues for innovative treatment strategies to combat this relentless brain tumor. The insights gained from this study may contribute to improved patient outcomes and revolutionize the landscape of glioblastoma therapy.

Keywords

cell viability, glioblastoma cell line, GBM, madecassic acid, oxidative stress.

References

• Ahiskali, I., Ferah Okkay, I., Mammadov, R., Okkay, U., Keskin Cimen, F., Kurt, N., & Suleyman, H. (2021). Effect of taxifolin on cisplatin-associated oxidative optic nerve damage in rats. Cutan Ocul Toxicol, 40(1), 1-6. doi:10.1080/15569527.2020.1844726
• Arancibia-Radich, J., Gonzalez-Blazquez, R., Alcala, M., Martin-Ramos, M., Viana, M., Arribas, S., . . . Gil-Ortega, M. (2019). Beneficial effects of murtilla extract and madecassic acid on insulin sensitivity and endothelial function in a model of diet-induced obesity. Sci Rep, 9(1), 599. doi:10.1038/s41598-018-36555-1
• Ferah Okkay, I., Okkay, U., Aydin, I. C., Bayram, C., Ertugrul, M. S., Mendil, A. S., & Hacimuftuoglu, A. (2022). Centella asiatica extract protects against cisplatin-induced hepatotoxicity via targeting oxidative stress, inflammation, and apoptosis. Environ Sci Pollut Res Int, 29(22), 33774-33784. doi:10.1007/s11356-022-18626-z
• Ferah Okkay, I., Okkay, U., Bayram, C., Cicek, B., Sezen, S., Aydin, I. C., . . . Hacimuftuoglu, A. (2023). Bromelain protects against cisplatin-induced ocular toxicity through mitigating oxidative stress and inflammation. Drug Chem Toxicol, 46(1), 69-76. doi:10.1080/01480545.2021.2011308
• Ferah Okkay, I., Okkay, U., Cicek, B., Yilmaz, A., Yesilyurt, F., Mendil, A. S., & Hacimuftuoglu, A. (2021). Neuroprotective effect of bromelain in 6-hydroxydopamine induced in vitro model of Parkinson's disease. Mol Biol Rep, 48(12), 7711-7717. doi:10.1007/s11033-021-06779-y
• Ferah Okkay, I., Okkay, U., Gundogdu, O. L., Bayram, C., Mendil, A. S., Ertugrul, M. S., & Hacimuftuoglu, A. (2022). Syringic acid protects against thioacetamide-induced hepatic encephalopathy: Behavioral, biochemical, and molecular evidence. Neurosci Lett, 769, 136385. doi:10.1016/j.neulet.2021.136385
• Liu, H., Qiu, W., Sun, T., Wang, L., Du, C., Hu, Y., . . . Sun, H. (2022). Therapeutic strategies of glioblastoma (GBM): The current advances in the molecular targets and bioactive small molecule compounds. Acta Pharm Sin B, 12(4), 1781-1804. doi:10.1016/j.apsb.2021.12.019
• Okkay, U., Ferah Okkay, I., Aydin, I. C., Bayram, C., Ertugrul, M. S., Gezer, A., & Hacimuftuoglu, A. (2021). Effects of Achillea millefolium on cisplatin induced ocular toxicity: an experimental study. Cutan Ocul Toxicol, 40(3), 214-220. doi:10.1080/15569527.2021.1919137
• Okkay, U., Ferah Okkay, I., Cicek, B., Aydin, I. C., Ertugrul, M. S., Bayram, C., . . . Hacimuftuoglu, A. (2021). Achillea millefolium alleviates testicular damage in paclitaxel-intoxicated rats via attenuation of testicular oxido-inflammatory stress and apoptotic responses. Andrologia, 53(5), e14028. doi:10.1111/and.14028
• Okkay, U., Ferah Okkay, I., Cicek, B., Aydin, I. C., & Ozkaraca, M. (2022). Hepatoprotective and neuroprotective effect of taxifolin on hepatic encephalopathy in rats. Metab Brain Dis, 37(5), 1541-1556. doi:10.1007/s11011-022-00952-3
• Shergalis, A., Bankhead, A., 3rd, Luesakul, U., Muangsin, N., & Neamati, N. (2018). Current Challenges and Opportunities in Treating Glioblastoma. Pharmacol Rev, 70(3), 412-445. doi:10.1124/pr.117.014944
• Sun, B., Wu, L., Wu, Y., Zhang, C., Qin, L., Hayashi, M., . . . Liu, T. (2020). Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review. Front Pharmacol, 11, 568032. doi:10.3389/fphar.2020.568032
• Ulasov, I., Singh, V., Laevskaya, A., Timashev, P., & Kharwar, R. K. (2023). Inflammatory Mediators and GBM Malignancy: Current Scenario and Future Prospective. Discov Med, 35(177), 458-475. doi:10.24976/Discov.Med.202335177.47
• Valdeira, A. S. C., Darvishi, E., Woldemichael, G. M., Beutler, J. A., Gustafson, K. R., & Salvador, J. A. R. (2019). Madecassic Acid Derivatives as Potential Anticancer Agents: Synthesis and Cytotoxic Evaluation. J Nat Prod, 82(8), 2094-2105. doi:10.1021/acs.jnatprod.8b00864
• Valdeira, A. S. C., Ritt, D. A., Morrison, D. K., McMahon, J. B., Gustafson, K. R., & Salvador, J. A. R. (2018). Synthesis and Biological Evaluation of New Madecassic Acid Derivatives Targeting ERK Cascade Signaling. Front Chem, 6, 434. doi:10.3389/fchem.2018.00434
• Won, J. H., Shin, J. S., Park, H. J., Jung, H. J., Koh, D. J., Jo, B. G., . . . Lee, K. T. (2010). Anti-inflammatory effects of madecassic acid via the suppression of NF-kappaB pathway in LPS-induced RAW 264.7 macrophage cells. Planta Med, 76(3), 251-257. doi:10.1055/s-0029-1186142
• Wu, W., Klockow, J. L., Zhang, M., Lafortune, F., Chang, E., Jin, L., . . . Daldrup-Link, H. E. (2021). Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance. Pharmacol Res, 171, 105780. doi:10.1016/j.phrs.2021.105780
• Xia, B., Bai, L., Li, X., Xiong, J., Xu, P., & Xue, M. (2015). Structural analysis of metabolites of asiatic acid and its analogue madecassic acid in zebrafish using LC/IT-MSn. Molecules, 20(2), 3001-3019. doi:10.3390/molecules20023001
• Yang, B., Xu, Y., Hu, Y., Luo, Y., Lu, X., Tsui, C. K., . . . Liang, X. (2016). Madecassic Acid protects against hypoxia-induced oxidative stress in retinal microvascular endothelial cells via ROS-mediated endoplasmic reticulum stress. Biomed Pharmacother, 84, 845-852. doi:10.1016/j.biopha.2016.10.015
• Zhang, H., Zhang, M., Tao, Y., Wang, G., & Xia, B. (2014). Madecassic acid inhibits the mouse colon cancer growth by inducing apoptosis and immunomodulation. J BUON, 19(2), 372-376. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24965394