Boric Acid Enhances Migration and Cytoskeletal Organization in T98G Cells: Against The Effects of Imatinib

Didem Mimiroğlu; Deniz Çabuk; Merve Akkulak

doi:10.17776/csj.1671321

Boric Acid Enhances Migration and Cytoskeletal Organization in T98G Cells: Against The Effects of Imatinib

Abstract

Imatinib is one of the Food and Drug Administration approved tyrosine-kinase inhibitors and widely used for the treatment of various cancers. During its use for treatment, mild to moderate side effects which affect neural cells and tissues, are commonly experienced by many patients. Boric acid is a trace element found in living organisms and many beneficial effects on the healing of the damaged cells and tissues are reported in literature. Although there are numerous studies in literature that include individually applications of imatinib and boric acid, there is no study examining their combined effects on T98G glioblastoma cells. Towards this goal, the present study aimed to evaluate the effects of the combined treatment of imatinib (5 M) and boric acid (15 mM) on T98G cells. The results showed that cellular migration increased 2-fold (p < 0.01), cellular morphology exhibited a spindle-shaped morphology and MAP2 expression levels and f-actin intensity were 1.5-fold higher for the combined treatment compared to only imatinib administration. The results cumulatively showed that the adverse effects of imatinib on T98G cells were reduced with boric acid and the biological properties of these cells were improved.

Keywords

Project Number

TUBITAK-217M952 project number

Thanks

The authors would like to thank Biological Sciences Department of METU and Orhan Adalı’s Laboratory in METU-Biological Sciences Department for the all experiments.

References

[1] Ertmer A., Huber V., Gilch S., Yoshimori T., Erfle V., Duyster J., Elsässer H.P., Schäzl H.M., The Anticancer Drug Imatinib Induces Cellular Autophagy, Leukemia, 21 (5) (2007) 936–942.
[2] Kim K.J., Jung J.M., Cho J.Y., Woo S.Y., Cho K.A., Ryu K.H., Yoo E.S., Antitumor Effects of Imatinib Mesylate and Synergistic Cytotoxicity with an Arsenic Compound in Neuroblastoma Cell Lines, Exp. Ther. Med., 2 (3) (2011) 557–561.
[3] Al-Hadiya B.M.H., Bakheit A.H.H., Abd-Elgalil A.A., Imatinib Mesylate. In: Profiles of Drug Substances, Excipients and Related Methodology, 1st ed. Elsevier Inc., (2014) 265-297.
[4] Kumar M., Kulshrestha R., Singh N., Jaggi A.S., Expanding Spectrum of Anticancer Drug, Imatinib, in the Disorders Affecting Brain and Spinal Cord, Pharmacol. Res., 143 (2019) 86–96.
[5] Jain P., Konoplev S., Benjamini O., Romagura J., Burger J.A., Long-Term Control of Refractory Follicular Lymphoma After Treatment of Secondary Acute Promyelocytic Leukemia with Arsenic Trioxide (As₂O₃) and All-Trans Retinoic Acid (ATRA), Blood Res., 53 (2) (2018) 169–172.
[6] Aras Y., Erguven M., Aktas E., Yazihan N., Bilir A., Antagonist Activity of the Antipsychotic Drug Lithium Chloride and the Antileukemic Drug Imatinib Mesylate During Glioblastoma Treatment In Vitro, Neurol. Res., 38 (9) (2016) 766–774.
[7] Shyam Sunder S., Sharma U.C., Pokharel S., Adverse Effects of Tyrosine Kinase Inhibitors in Cancer Therapy: Pathophysiology, Mechanisms and Clinical Management, Signal Transduct. Target. Ther., 8 (1) (2023) 262.
[8] Schiff D., Wen P.Y., van den Bent M.J., Neurological Adverse Effects Caused by Cytotoxic and Targeted Therapies, Nat. Rev. Clin. Oncol., 6 (10) (2009) 596–603.

[9] Lixi F., Giannaccare G., Salerno G., Gagliardi V., Pellegrino A., Vitiello L., Side Effects of Novel Anticancer Drugs on the Posterior Segment of the Eye: A Review of the Literature, J. Pers. Med., 14 (12) (2024) 1160.
[10] Rotstein D.L., Sawicka K., Bharatha A., Montalban X., Lipton J.H., CNS Demyelination After Initiating the Tyrosine Kinase Inhibitor Imatinib: A Report of Two Cases, Mult. Scler. J., 26 (9) (2020) 1121–1124.
[11] Pizzorno L., Nothing Boring About Boron, Integr. Med.: A Clinician’s Journal, 14 (4) (2015) 35–48.
[12] Hilal B., Eldem A., Oz T., Pehlivan M., Pirim I., Boric Acid Affects Cell Proliferation, Apoptosis, and Oxidative Stress in ALL Cells, Biol. Trace Elem. Res., 202 (8) (2024) 3614–3622.
[13] Turkez H., Alper F., Bayram C., Baba C., Yıldız E., Saracoglu M., Kucuk M., Gozegir B., Kiliclioglu M., Yeşilyurt M., Tozlu O.O., Bolat I., Yildirim S., Barutcigil M.F., Isik F., Kiki Ö., Aydın F., Arslan M.E., Cadircı K., Karaman A., Tatar A., Hacımüftüoğlu A., Boric Acid Impedes Glioblastoma Growth in a Rat Model: Insights from Multi-Approach Analysis, Med. Oncol., 42 (2) (2025) 1-17.
[14] Ataizi Z.S., Ozkoc M., Kanbak G., Karimkhani H., Donmez D.B., Ustunisik N., Ozturk B., Evaluation of the Neuroprotective Role of Boric Acid in Preventing Traumatic Brain Injury-Mediated Oxidative Stress, Turk. Neurosurg., 31 (4) (2021) 493–499.
[15] Ozdemir H.S., Yunusoglu O., Sagmanligil V., Yasar S., Colcimen N., Goceroglu R.T., Catalkaya E., Investigation of the Pharmacological, Behavioral and Biochemical Effects of Boron on Rats with Rotenone-Induced Parkinson’s Disease, Cell. Mol. Biol., 68 (8) (2022) 13–21.
[16] Kiseleva, L. N., Kartashev, A. V., Vartanyan, N. L., Pinevich, A. A., Samoilovich, M. P. A172 and T98G cell lines characteristics. Cell and Tissue Biology, 10 (5) (2016) 341-348.
[17] Kiseleva, L. N., Kartashev, A. V., Vartanyan, N. L., Pinevich, A. A., Filatov, M. V., Samoilovich, M. P. Characterization of new human glioblastoma cell lines. Cell and Tissue Biology, 12 (1) (2018) 1-6.
[18] Fuster, E., Candela, H., Estévez, J., Vilanova, E., Sogorb, M. A. A Transcriptomic Analysis of T98G Human Glioblastoma Cells after Exposure to Cadmium-Selenium Quantum Dots Mainly Reveals Alterations in Neuroinflammation Processes and Hypothalamus Regulation. International Journal of Molecular Sciences, 23 (4) (2022) 2267.
[19] Fabbri, R., Cacopardo, L., Ahluwalia, A., Magliaro, C. Advanced 3D models of human brain tissue using neural cell lines: state-of-the-art and future prospects. Cells, 12 (8) (2023) 1181.
[20] de Joannon, A. C., Mancini, F., Landolfi, C., Soldo, L., Leta, A., Ruggieri, A., Mangano, G., Polenzani, L., Pinza, M., Milanese, C. Adenosine triphosphate affects interleukin-1β release by T98G glioblastoma cells through a purinoceptor-independent mechanism. Neuroscience letters, 285 (3) (2000) 218-222.
[21] Fuster, E., Candela, H., Estévez, J., Arias, A. J., Vilanova, E., Sogorb, M. A. Effects of silver nanoparticles on T98G human glioblastoma cells. Toxicology and Applied Pharmacology, 404, (2020) 115178.
[22] Perego C., Vanoni C., Massari S., Raimondi A., Pola S., Cattaneo M.G., Francolini M., Vicentini L.M., Pietrini G., Invasive Behaviour of Glioblastoma Cell Lines is Associated with Altered Organisation of the Cadherin-Catenin Adhesion System, J. Cell Sci., 115 (16) (2002) 3331–3340.
[23] Al-Nasiry, S., Geusens, N., Hanssens, M., Luyten, C., & Pijnenborg, R. The use of Alamar Blue assay for quantitative analysis of viability, migration and invasion of choriocarcinoma cells. Human reproduction, 22 (5) (2007) 1304-1309.
[24] Mimiroglu, D., Tufan, Y., Yanik, T., & Ercan, B. Synergistic effect of nanostructured topography and CNF incorporation into silk fibroin films enhances mouse neuroblastoma cell functions. Surfaces and Interfaces, 45 (2024) 103876.
[25] Mahmood, T., Yang, P. C. Western blot: technique, theory, and trouble shooting. North American journal of medical sciences, 4 (9) (2012) 429.
[26] Vang Mouritzen M., Jenssen H., Optimized Scratch Assay for In Vitro Testing of Cell Migration with an Automated Optical Camera, J. Vis. Exp., 138 (2018) 57691.
[27] Lu J., Hu Y., Qian R., Zhang Y., Yang X., Luo P., Enhanced Proliferation Inhibition and Apoptosis in Glioma Cells Elicited by Combination of Irinotecan and Imatinib, Eur. J. Pharmacol., 874 (2020) 173022.
[28] Ren H., Tan X., Dong Y., Giese A., Chou T.C., Rainov N., Yang B., Differential Effect of Imatinib and Synergism of Combination Treatment with Chemotherapeutic Agents in Malignant Glioma Cells, Basic Clin. Pharmacol. Toxicol., 104 (3) (2009) 241–252.
[29] Ranza E., Mazzini G., Facoetti A., Nano R., In-Vitro Effects of the Tyrosine Kinase Inhibitor Imatinib on Glioblastoma Cell Proliferation, J. Neurooncol., 96 (2010) 349–357.
[30] Demestre M., Herzberg J., Holtkamp N., Hagel C., Reuss D., Friedrich R.E., Kluwe L., Von Deimling A., Mautner V.F., Kurtz A., Imatinib Mesylate (Glivec) Inhibits Schwann Cell Viability and Reduces the Size of Human Plexiform Neurofibroma in a Xenograft Model, J. Neurooncol., 98 (2010) 11–19.
[31] Turkez H., Arslan M.E., Tatar A., Mardinoglu A., Promising Potential of Boron Compounds Against Glioblastoma: In Vitro Antioxidant, Anti-Inflammatory and Anticancer Studies, Neurochem. Int., 149 (2021) 105137.
[32] Melak M., Plessner M., Grosse R., Actin Visualization at a Glance, J. Cell Sci., 130 (3) (2017), 525–530.
[33] Zonderland J., Wieringa P., Moroni L., A Quantitative Method to Analyse F-Actin Distribution in Cells, MethodsX, 6 (2019) 2562–2569.
[34] Glushakova O.Y., Glushakov A.V., Mannix R., Miller E.R., Valadka A.B., Hayes R.L. The Use of Blood-Based Biomarkers to Improve the Design of Clinical Trials of Traumatic Brain Injury. In: Handbook of Neuroemergency Clinical Trials. 2nd ed. Elsevier, (2017) 139-166.
[35] Mondello S., Hayes R.L., Biomarkers. In: Handbook of Clinical Neurology, Vol. 127. Elsevier, (2015) 245–265.
[36] Mondello S., Gabrielli A., Catani S., D’Ippolito M., Jeromin A., Ciaramella A., Bossù P., Schmid K., Tortella F., Wang K.K.W., Hayes R.L., Formisano R., Increased Levels of Serum MAP-2 at 6-Months Correlate with Improved Outcome in Survivors of Severe Traumatic Brain Injury, Brain Inj., 26 (13-14) (2012) 1629–1635.
[37] Grada A., Otero-Vinas M., Prieto-Castrillo F., Obagi Z., Falanga V., Research Techniques Made Simple: Analysis of Collective Cell Migration Using the Wound Healing Assay, J. Invest. Dermatol., 137 (2) (2017) e11–e16.
[38] Stamm A., Reimers K., Strauß S., Vogt P., Scheper T., Pepelanova I., In Vitro Wound Healing Assays – State of the Art, BioNanoMaterials, 17 (1-2) (2016) 79–87.
[39] Demirci S., Doğan A., Aydın S., Dülger E.Ç., Şahin F., Boron Promotes Streptozotocin-Induced Diabetic Wound Healing: Roles in Cell Proliferation and Migration, Growth Factor Expression, and Inflammation, Mol. Cell. Biochem., 417 (2016) 119–133.
[40] Tepedelen B.E., Soya E., Korkmaz M., Boric Acid Reduces the Formation of DNA Double Strand Breaks and Accelerates Wound Healing Process, Biol. Trace Elem. Res., 174 (2016) 309–318.

Details

Primary Language

English

Subjects

Cell Development, Proliferation and Death , Biochemistry and Cell Biology (Other)

Journal Section

Research Article

Authors

Didem Mimiroğlu ^*
0000-0003-2838-9719
Türkiye

Deniz Çabuk
0000-0002-8874-0876
Türkiye

Merve Akkulak
0000-0003-2834-7682
Türkiye

Publication Date

September 30, 2025

Submission Date

April 7, 2025

Acceptance Date

July 18, 2025

Published in Issue

Year 2025 Volume: 46 Number: 3

DOI

https://doi.org/10.17776/csj.1671321

IZ

https://izlik.org/JA79LW72UY

Cite

RIS / Bibtex

APA

Mimiroğlu, D., Çabuk, D., & Akkulak, M. (2025). Boric Acid Enhances Migration and Cytoskeletal Organization in T98G Cells: Against The Effects of Imatinib. Cumhuriyet Science Journal, 46(3), 471-477. https://doi.org/10.17776/csj.1671321