Anticancer Effects of Alpha-lipoic Acid on A172 and U373 Human Glioblastoma Cells

Year 2023, Volume: 13 Issue: 2, 851 - 857, 01.06.2023

Doğukan Mutlu , Mücahit Seçme , Şevki Arslan

https://doi.org/10.21597/jist.1181520

Cited By: 1

Abstract

The high mortality rate of Glioblastoma multiforme (GBM) patients is partly due to the invasive behavior of the tumor cells. Given the increased resistance to conventional therapies of invasive cells after surgical operations, current treatments are ineffective. Therefore, understanding the mechanisms of GBM cell invasion is critical for the development of successful therapeutic approaches. Natural small molecules and metabolites are widely used as chemotherapeutic and adjuvant agents in cancer treatments because they have strong anticancer properties and minimal side effects. Alpha-lipoic acid (ALA) is an antioxidant that has been found to reduce the level of ROS and increase GPx activity in cancer patients. In this study, we analyzed the in-vitro cytotoxic potential and apoptotic effect in A172 and U373 cells in the presence of various concentrations (7.8-500 µM) of ALA. We also investigated scratch assay in both cell lines. The ALA inhibited cell viability of A172 and U373 cells at 48h. In addition, Bax mRNA expression was significantly increased in response to ALA for A172 cells. Furthermore, the BCL-2 level was decreased in A172 cells with ALA after 48h. Caspase 3 and 9 mRNA expressions were increased in ALA treated U373 cell line. In summary, we found that ALA inhibits cell growth and causes apoptosis in A172 and U373 glioblastoma cells.

Keywords

alpha-Lipoic acid, anticancer, glioblastoma, wound healing, RT-PCR

Project Number

PAU-BAP-2018-KRM-011

References

• Alpay, M., Yurdakok-Dikmen, B., Kismali, G., Sel, T. (2016). Antileukemic Effects of Piperlongumine and Alpha Lipoic Acid Combination on Jurkat, MEC1 and NB4 Cells in vitro. Journal of Cancer Research and Therapeutics, 12(2), 556–560.
• Attia, M., Essa, E. A., Zaki, R. M., Elkordy, A. A. (2020). An Overview of the Antioxidant Effects of Ascorbic Acid and Alpha Lipoic Acid (in Liposomal Forms) as Adjuvant in Cancer Treatment. Antioxidants, 9(5), 359.
• Bramanti, V., Tomassoni, D., Bronzi, D., Grasso, S., Currò, M., Avitabile, M., Volsi L. G., Renis, M., Ientile, R., Amenta, F., Avola, R. (2010). Alpha-lipoic acid modulates GFAP, vimentin, nestin, cyclin D1 and MAP-kinase expression in astroglial cell cultures. Neurochemical Research, 35(12), 2070–2077.
• Choi, S. Y., Yu, J. H., Kim, H. (2009). Mechanism of Alpha-lipoic Acid-induced Apoptosis of Lung Cancer Cells. Annals of the New York Academy of Sciences, 1171, 149-55.
• Ellis, H. P., Greenslade, M., Powell, B., Spiteri, I., Sottoriva, A., Kurian, K. M. (2015). Current Challenges in Glioblastoma: Intratumour Heterogeneity, Residual Disease, and Models to Predict Disease Recurrence. Frontiers in Oncology, 5, 251.
• Hitoshi, Y., Lorens, J., Kitada, S. I., Fisher, J., LaBarge, M., Ring, H.Z., Francke, U., Reed, J.C., Kinoshita, S., Nolan, G. P. (1998). Toso, a Cell Surface, Specific Regulator of Fas-induced Apoptosis in T Cells. Immunity, 8, 461–71.
• Hongmei, Z. (2012). Extrinsic and Intrinsic Apoptosis Signal Pathway Review. In (Ed.), Apoptosis and Medicine. IntechOpen.
• Khasraw, M., Fujita, Y., Lee-Chang, C., Balyasnikova, I. V., Najem, H., Heimberger, A. B. (2022). New Approaches to Glioblastoma. Annual Review of Medicine, 73, 279–292.
• Konus, M., Cetin, D., Kızılkan, N. D., Yılmaz, C., Fidan, C., Algso, M., Kavak, E., Kivrak, A., Kurt-Kızıldogan, A., Otur, C., Mutlu, D., Abdelsalam, A. H., Arslan, S. (2022). Synthesis and Biological Activity of New Indole Based Derivatives as Potent Anticancer, Antioxidant and Antimicrobial Agents. Journal of Molecular Structure, 1263, 133168.
• Liu, J. Y., Fu, W. Q., Zheng, X. J., Li, W., Ren, L. W., Wang, J. H., Yang, C., Du, G. H. (2021). Avasimibe Exerts Anticancer Effects on Human Glioblastoma Cells via Inducing Cell Apoptosis and Cell Cycle Arrest. Acta Pharmacologica Sinica, 42(1), 97–107.
• Moungjaroen, J., Nimmannit, U., Callery, P. S., Wang, L., Azad, N., Lipipun, V., Chanvorachote, P., Rojanasakul, Y. (2006). Reactive Oxygen Species Mediate Caspase Activation and Apoptosis Induced by Lipoic Acid in Human Lung Epithelial Cancer Cells Through Bcl-2 Down-regulation. The Journal of Pharmacology and Experimental Therapeutics, 319(3), 1062–1069.
• Mutlu, D., Cakir, C., Ozturk, M., Arslan, S. (2022). Anticancer and Apoptotic Effects of a Polysaccharide Extract Isolated from Lactarius chrysorrheus Fr. in HepG2 and PANC-1 Cell Lines. Archives of Biological Sciences, 74(4), 315-24.
• Na, M. H., Seo, E. Y., Kim, W. K. (2009). Effects of α-lipoic Acid on Cell Proliferation and apoptosis in MDA-MB-231 Human Breast Cells. Nutrition Research and Practice, 3(4), 265.
• Ostrom, Q. T., Gittleman, H., Truitt, G., Boscia, A., Kruchko, C., Barnholtz-Sloan, J. S. (2021). CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2011-2015. Neuro-Oncology, 23, 12.
• Packer, L. (1998). Alpha-Lipoic Acid: A Metabolic Antioxidant Which Regulates NF-kappa B Signal Transduction and Protects Against Oxidative Injury. Drug Metabolism Reviews, 30, 245–275.
• Puchsaka, P., Chaotham, C., Chanvorachote, P. (2016). α-Lipoic Acid Sensitizes Lung Cancer Cells to Chemotherapeutic Agents and Anoikis via Integrin β1/β3 Downregulation. International Journal of Oncology, 49, 1445-1456.
• Sahin, C., Mutlu, D., Nasirli, F., Mahmoudi, G., Zubkov, F. I., Arslan, S., Doğan, N. M. (2021). New Iridium Bis‐terpyridine Complexes: Synthesis, Characterization, Antibiofilm and Anticancer potentials. Biometals, 34, 701–713.
• Simbula, G., Columbano, A., Ledda-Columbano, G. M., Sanna, L., Deidda, M., Diana. A., Pibiri, M. (2007). Increased ROS Generation and p53 Activation in Alpha-lipoic Acid-induced Apoptosis of Hepatoma Cells. Apoptosis: An International Journal on Programmed Cell Death, 12(1), 113–123.
• Tripathy, J., Tripathy, A., Thangaraju, M., Suar, M., Elangovan, S. (2018). α-Lipoic Acid Inhibits the Migration and Invasion of Breast Cancer Cells Through Inhibition of TGFβ Signaling. Life Sciences, 207, 15-22.
• Vig-Varga, E., Benson, E. A., Limbil, T. L., Allison, B. M., Geobl, M. G., Harrington, M. A. (2006). Alpha-lipoic Acid Modulate Ovarian Surface Epithelial Cell Growth. Gynecologic Oncology, 103, 45–52.
• Wang, G., Wang, W. (2022). Advanced Cell Therapies for Glioblastoma. Frontiers in Immunology, 13, 904133.
• Wang, R., Zhang, L., Liao, R., Li, Q., Pi, R., Yang, X. (2019). N2L, a novel lipoic acid-niacin dimer protects HT22 cells against β-amyloid peptide-induced damage through attenuating apoptosis. Metabolic Brain Disease, 34(6), 1761-1770.
• Wenzel, U., Nickel, A., Daniel, H. (2005). Alpha-Lipoic Acid Induces Apoptosis in Human Colon Cancer Cells by Increasing Mitochondrial Respiration with a Concomitant O2-*- Generation. Apoptosis, 10, 359–368.
• Yamaguchi, H., Wyckoff, J., Condeelis, J. (2005). Cell Migration in Tumors. Current Opinion in Cell Biology, 17(5), 559-64.
• Yang, E., Zha, J., Jockel, J., Boise, L. H., Thompson, C. B., Korsmeyer, S. J. (1995). Bad, a Heterodimeric Partner for Bcl-XL and Bcl-2, Displaces Bax and Promotes Cell Death. Cell, 80, 285–91.
• Yoo, T. H., Lee, J. H., Chun, H. S., Chi, S. G. (2013). α-Lipoic Acid Prevents p53 Degradation in Colon Cancer cells by Blocking NF-κB Induction of RPS6KA4. Anticancer Drugs, 24(6), 555–565.