Bisphenols S and F drive ovarian granulosa cell tumor invasion via a metabolic switch

• Published in: Toxicology letters Vol. 375; pp. 39 - 47
• Main Authors: Gogola-Mruk, Justyna, Krawczyk, Kinga, Marynowicz, Weronika, Rokita, Magdalena, Nimpsz, Samantha, Ptak, Anna
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2023
• Subjects: Adult; Benzhydryl Compounds - metabolism; Bisphenol S and F; Cell Line, Tumor; Environmental Pollutants; Female; Glucose; Glucose uptake; Glycolysis; Granulosa Cell Tumor; Granulosa Cells - metabolism; Humans; Spheroid invasion; Glycolysis; Glucose uptake; Granulosa cell tumor; Spheroid invasion; Bisphenol S and F
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2022.12.011

Alterations in the metabolism of cancer cells are crucial for tumor growth and progression. However, the mechanism whereby environmental pollutants such as bisphenols F (BPF) and S (BPS) affect glucose metabolism through the glycolytic pathway, and therefore influence tumor progression, are unclear. Both bisphenols are endocrine-disrupting molecules that are used in plastics. As a consequence of their widespread use, these compounds have been detected in various human body fluids. Thus, hormone-sensitive cancers, such as ovarian cancers, are exposed to these compounds. In the present study, we aimed to determine the effects of the concentrations of BPS and BPF found in body fluids on the cell viability, glucose uptake, glycolysis, oxygen consumption, and invasion by the adult ovarian granulosa cell tumor (AGCT) cell line. We found that BPS and BPF increased the glucose uptake, hexokinase activity, proliferation, and invasion of the cells at environmentally relevant concentrations. Furthermore, we identified an inhibition of glycolysis in parallel with an increase in oxygen consumption, suggesting a BPS/BPF-induced switch from aerobic glycolysis to mitochondrial respiration. In summary, these findings demonstrate a new mechanism through which BPS and BPF promote ovarian granulosa cell tumor progression by increasing energy production through mitochondrial respiration. Thus, both bisphenols induced a metabolic switch that appears to be a stimulus for AGCT progression. [Display omitted] •Bisphenols F (BPF) and S (BPS) promote tumor progression.•Both induce proliferation and invasion by an adult ovarian granulosa tumor cell line.•BPS and BPF increase the glucose uptake and hexokinase activity of these cells.•Both chemicals inhibit glycolysis and increase oxygen consumption.•Inhibition of glucose uptake or mitochondrial respiration inhibits tumor cell invasion.