Molecules (Jun 2024)

Halogenated Boroxine K<sub>2</sub>[B<sub>3</sub>O<sub>3</sub>F<sub>4</sub>OH] Modulates Metabolic Phenotype and Autophagy in Human Bladder Carcinoma 5637 Cell Line

  • Nikolina Elez-Burnjaković,
  • Lejla Pojskić,
  • Anja Haverić,
  • Naida Lojo-Kadrić,
  • Maida Hadžić Omanović,
  • Ajla Smajlović,
  • Svetoslav Kalaydjiev,
  • Milka Maksimović,
  • Bojan Joksimović,
  • Sanin Haverić

DOI
https://doi.org/10.3390/molecules29122919
Journal volume & issue
Vol. 29, no. 12
p. 2919

Abstract

Read online

Halogenated boroxine K2[B3O3F4OH] (HB), an inorganic derivative of cyclic anhydride of boronic acid, is patented as a boron-containing compound with potential for the treatment of both benign and malignant skin changes. HB has effectively inhibited the growth of several carcinoma cell lines. Because of the growing interest in autophagy induction as a therapeutic approach in bladder carcinoma (BC), we aimed to assess the effects of HB on metabolic phenotype and autophagy levels in 5637 human bladder carcinoma cells (BC). Cytotoxicity was evaluated using the alamar blue assay, and the degree of autophagy was determined microscopically. Mitochondrial respiration and glycolysis were measured simultaneously. The relative expression of autophagy-related genes BECN1, P62, BCL-2, and DRAM1 was determined by real-time PCR. HB affected cell growth, while starvation significantly increased the level of autophagy in the positive control compared to the basal level of autophagy in the untreated negative control. In HB-treated cultures, the degree of autophagy was higher compared to the basal level, and metabolic phenotypes were altered; both glycolysis and oxidative phosphorylation (OXPHOS) were decreased by HB at 0.2 and 0.4 mg/mL. Gene expression was deregulated towards autophagy induction and expansion. In conclusion, HB disrupted the bioenergetic metabolism and reduced the intracellular survival potential of BC cells. Further molecular studies are needed to confirm these findings and investigate their applicative potential.

Keywords