Promising potential of boron compounds against Glioblastoma: In Vitro antioxidant, anti-inflammatory and anticancer studies

Neurochem Int. 2021 Oct;149:105137. doi: 10.1016/j.neuint.2021.105137. Epub 2021 Jul 19.

Abstract

Glioblastoma (GB) is the most common and aggressive primary malignant astrocytoma correlated with poor patient survival. There are no curative treatments for GB, and it becomes resistant to chemotherapy, radiation therapy, and immunotherapy. Resistance in GB cells is closely related to their states of redox imbalance, and the role of reactive oxygen species and its impact on cancer cell survival is still far from elucidation. Boron-containing compounds, especially boric acid (BA) and borax (BX) exhibited interesting biological effects involving antibacterial, antiviral, anti-cancerogenic, anti-mutagenic, anti-inflammatory as well as anti-oxidative features. Recent studies indicated that certain boron compounds could be cytotoxic on human GB. Nevertheless, there is gap of knowledge in the literature on exploring the underlying mechanisms of anti-GB action by boron compounds. Here, we identified and compared the potential anti-GB effect of both BA and BX, and revealed their underlying anti-GB mechanism. We performed cell viability, oxidative alterations, oxidative DNA damage potential assays, and explored the inflammatory responses and gene expression changes by real-time PCR using U-87MG cells. We found that BA and BX led to a remarkable reduction in U-87MG cell viability in a concentration-dependent manner. We also found that boron compounds increased the total oxidative status and MDA levels along with the SOD and CAT enzyme activities and decreased total antioxidant capacity and GSH levels in U-87MG cells without inducing DNA damage. The cytokine levels of cancer cells were also altered. We verified the selectivity of the compounds using a normal cell line, HaCaT and found an exact opposite condition after treating HaCaT cells with BA and BX. BA applications were more effective than BX on U-87MG cell line in terms of increasing MDA levels, SOD and CAT enzyme activities, and decreasing Interleukin-1α, Interleukin-6 and Tumor necrosis factor- α (TNF- α) levels. We finally observed that anticancer effect of BA and BX were associated with the BRAF/MAPK, PTEN and PI3K/AKT signaling pathways in respect of downregulatory manner. Especially, BA application was found more favorable because of its inhibitory effect on PIK3CA, PIK3R1, PTEN and RAF1 genes. In conclusion, our analysis indicated that boron compounds may be safe and promising for effective treatment of GB.

Keywords: Anticancer; Borax; Boric acid; Boron; Cytotoxicity; Gene expression; Glioblastoma; Inflammatory response; Oxidative alteration.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Borates / pharmacology
  • Borates / therapeutic use
  • Boric Acids / pharmacology
  • Boric Acids / therapeutic use
  • Boron Compounds / pharmacology
  • Boron Compounds / therapeutic use*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Glioblastoma / drug therapy
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Antioxidants
  • Borates
  • Boric Acids
  • Boron Compounds
  • Inflammation Mediators
  • borax
  • sodium borate
  • boric acid