AI Article Synopsis
- Glioblastomas (GBs) are aggressive brain tumors that are influenced by the steroid hormone progesterone (P4) and its metabolite, allopregnanolone (3α-THP), which enhance cell growth and movement.
- Research shows that 3α-THP increases the migration and invasion of various human GB cell lines (U251, U87, and LN229) at a concentration of 100 nM and that GB cells have higher levels of enzymes (AKR1C1-4) involved in its metabolism compared to normal astrocytes.
- The study found that while silencing these enzymes did not affect 3α-THP’s impact on migration and invasion, the activation of the c-S
Article Abstract
Glioblastomas (GBs) are the most aggressive and common primary malignant brain tumors. Steroid hormone progesterone (P4) and its neuroactive metabolites, such as allopregnanolone (3α-THP) are synthesized by neural, glial, and malignant GB cells. P4 promotes cellular proliferation, migration, and invasion of human GB cells at physiological concentrations. It has been reported that 3α-THP promotes GB cell proliferation. Here we investigated the effects of 3α-THP on GB cell migration and invasion, the participation of the enzymes involved in its metabolism (AKR1C1-4), and the role of the c-Src kinase in 3α-THP effects in GBs. 3α-THP 100 nM promoted migration and invasion of U251, U87, and LN229 human-derived GB cell lines. We observed that U251, LN229, and T98G cell lines exhibited a higher protein content of AKR1C1-4 than normal human astrocytes. AKR1C1-4 silencing did not modify 3α-THP effects on migration and invasion. 3α-THP activated c-Src protein at 10 min (U251 cells) and 15 min (U87 and LN229 cells). Interestingly, the pharmacological inhibition of c-Src decreases the promoting effects of 3α-THP on cell migration and invasion. Together, these data indicate that 3α-THP promotes GB migration and invasion through c-Src activation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105169 | PMC |
| http://dx.doi.org/10.3390/ijms23094996 | DOI Listing |
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