Evaluation of the Antitumor Potential of Soloxolone Tryptamide against Glioblastoma Multiforme Using in silico, in vitro, and in vivo Approaches
-
Published:2023-07
Issue:7
Volume:88
Page:1008-1021
-
ISSN:0006-2979
-
Container-title:Biochemistry (Moscow)
-
language:en
-
Short-container-title:Biochemistry Moscow
Author:
Markov Andrey V.,Odarenko Kirill V.,Sen’kova Aleksandra V.,Ilyina Anna A.,Zenkova Marina A.
Abstract
Abstract
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by uncontrollable diffusive growth, resistance to chemo- and radiotherapy, and a high recurrence rate leading to a low survival rate of patients with GBM. Due to a large number of signaling pathways regulating GBM pathogenesis, one of the promising directions is development of novel anti-glioblastoma compounds based on natural metabolites capable of affecting multiple targets. Here, we investigated the antitumor potential of the semisynthetic triterpenoid soloxolone tryptamide (STA) against human glioblastoma U87 cells. STA efficiently blocked the growth of U87 cells in 2D and 3D cultures, enhanced adhesiveness of tumor cells, and displayed synergistic cytotoxicity with temozolomide. In silico analysis suggested that the anti-glioblastoma activity of STA can be explained by its direct interaction with EGFR, ERBB2, and AKT1 which play an important role in the regulation of GBM malignancy. Along with direct effect on U87 cells, STA normalized tumor microenvironment in murine heterotopic U87 xenograft model by suppressing the development of immature blood vessels and elastin production in the tumor tissue. Taken together, our results clearly demonstrate that STA can be a novel promising antitumor candidate for GMB treatment.
Publisher
Pleiades Publishing Ltd
Subject
Biochemistry,General Medicine,Biochemistry, Genetics and Molecular Biology (miscellaneous),Biophysics,Geriatrics and Gerontology
Reference54 articles.
1. Sanati, M., Binabaj, M. M., Ahmadi, S. S., Aminyavari, S., Javid, H., Mollazadeh, H., Bibak, B., Mohtashami, E., Jamialahmadi, T., Afshari, A. R., and Sahebkar, A. (2022) Recent advances in glioblastoma multiforme therapy: a focus on autophagy regulation, Biomed. Pharmacother., 155, 113740,
https://doi.org/10.1016/j.biopha.2022.113740. 2. Torrisi, F., Alberghina, C., D’Aprile, S., Pavone, A. M., Longhitano, L., Giallongo, S., Tibullo, D., Di Rosa, M., Zappalà, A., Cammarata, F. P., Russo, G., Ippolito, M., Cuttone, G., Li Volti, G., Vicario, N., and Parenti, R. (2022) The hallmarks of glioblastoma: heterogeneity, intercellular crosstalk and molecular signature of invasiveness and progression, Biomedicines, 10, 806,
https://doi.org/10.3390/biomedicines10040806. 3. Cha, G. D., Kang, T., Baik, S., Kim, D., Choi, S. H., Hyeon, T., and Kim, D.-H. (2020) Advances in drug delivery technology for the treatment of glioblastoma multiforme, J. Control. Release, 328, 350-367,
https://doi.org/10.1016/j.jconrel.2020.09.002. 4. Qazi, M. A., Vora, P., Venugopal, C., Sidhu, S. S., Moffat, J., Swanton, C., and Singh, S. K. (2017) Intratumoral heterogeneity: pathways to treatment resistance and relapse in human glioblastoma, Ann. Oncol., 28, 1448-1456,
https://doi.org/10.1093/annonc/mdx169. 5. Sestito, S., Runfola, M., Tonelli, M., Chiellini, G., and Rapposelli, S. (2018) New multitarget approaches in the war against glioblastoma: a mini-perspective, Front. Pharmacol., 9, 874,
https://doi.org/10.3389/fphar.2018.00874.
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|