The dual role of boron in vitro neurotoxication of glioblastoma cells via SEMA3F / NRP2 and ferroptosis signaling pathways

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Kar F., Hacioğlu C., Kaçar S.

ENVIRONMENTAL TOXICOLOGY AN INTERNATIONAL JOURNAL, vol.38, no.1, pp.70-77, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 38 Issue: 1
  • Publication Date: 2023
  • Doi Number: 10.1002/tox.23662
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, Compendex, EMBASE, Environment Index, Food Science & Technology Abstracts, Geobase, Greenfile, MEDLINE, Pollution Abstracts, Veterinary Science Database
  • Page Numbers: pp.70-77
  • Keywords: boric acid, brain tumor, cancer, cytotoxicity, ferroptosis, Semaphorin
  • Kütahya Health Sciences University Affiliated: Yes


Glioblastoma multiform (GBM) is a malignant tumor cancer that originates from the star-shaped glial support tissues, namely astrocytes, and it is associated with a poor prognosis in the brain. The GBM has no cure, and chemotherapy, radiation therapy, and immunotherapy are all ineffective. A certain dose of Boric acid (BA) has many biochemical effects, conspicuously over antioxidant/oxidant rates. This article sought to investigate the modifies of various doses of BA on the glioblastoma concerning cytotoxicity, ferroptosis, apoptosis, and semaphorin–neuropilin signaling pathway. The Cytotoxic activity and cell viability of BA (0.39–25 mM) in C6 cells were tested at 24, 48, and 72 h using 3-(4,5-dimethylthiazol, 2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The IC50 concentration of BA at 1.56 mM was found and cell lysate used for biochemical analysis. Glutathione peroxidase 4 (GPx4) and ACLS4 levels of ferroptosis, levels of total antioxidant (TAS) and oxidant (TAS) parameters, malondialdehyde (MDA), apoptotic proteins as caspase 3 (CASP3) and caspase 7 (CASP7) were measured. The ferroptosis, semaphoring–neuropilin, apoptotic pathway markers and cell counts were analyzed with flow cytometry, Q-PCR, Western and Elisa technique in the C6 cell lysate. BA triggered ferroptosis in the C6 cells dose-dependently, affecting the semaphorin pathway, so reducing proliferation with apoptotic compared with untreated cell as control group (p < .05). This study revealed that BA, defined as trace element and natural compound, incubated ferroptosis, total oxidant molecules, and caspase protein in a dose-dependently by disrupting SEMA3F in tumor cells