Reverted effect of mesenchymal stem cells in glioblastoma treated with agathisflavone and its selective antitumoral effect on cell viability, migration, and differentiation via STAT3

Glioblastoma is the most lethal tumor of the central nervous system, presenting a very poor prognostic, with a survival around 16 months. The interaction of mesenchymal stem cells and tumor cells has been studied, showing a bias in their role favoring or going against aggressiveness. Natural products such as flavonoids have showed their anticancer properties and the synergic potential with the activation of microenvironment cells to inhibit tumor progression. Agathisflavone is a flavonoid studied in neurodegenerative diseases and cancer. The present study investigated the effect of flavonoid in the viability of heterogeneous glioblastoma (GBM) cells considering a coculture or conditioned medium of mesenchymal stem cells (MSCs) effect, as well as the dose‐dependent effect of this flavonoid in tumor migration and differentiation via STAT3. Agathisflavone (3–10 μM) induced dose‐dependent toxicity to GL‐15 and U373 human GBM cells, since 24 h after treatments. It was not toxic to human MSC but modified the pattern of interaction with GBM cells. Agathisflavone also inhibited migration and increased differentiation of human GBM cells, associated with the reduction on the expression of STAT3. These results demonstrate that the flavonoid agathisflavone had a direct anti‐glioma effect. However, could be observed its effect in MSCs response that may have an impact in controlling GBM growth and aggressiveness, an important factor to consider for new therapies. Flavonoid agathisflavone selective induces dose‐dependent toxicity in GL‐15 and U373 human glioblastoma (GBM) cells. Agathisflavone inhibits migration and promotes differentiation of human GBM cells. Agathisflavone is not toxic to human mesenchymal stem cells but modifies the pattern of interaction with glioblastoma cells, resulting in resistance. Highlights Flavonoid agathisflavone selective induces dose‐dependent toxicity in GL‐15 and U373 human glioblastoma (GBM) cells. Agathisflavone inhibits migration and promotes differentiation of human GBM cells. Agathisflavone is not toxic to human mesenchymal stem cells but modifies the pattern of interaction with glioblastoma cells, resulting in resistance.