Abstract
BackgroundGlioblastoma (GB) cells have the ability to migrate and infiltrate the normal parenchyma, leading to the formation of recurrent tumors often adjacent to the surgical extraction site. We recently showed that Phoneutria nigriventer spider venom (PnV) has anticancer effects mainly on the migration of human GB cell lines (NG97 and U-251). The present work aimed to investigate the effects of isolated components from the venom on migration, invasiveness, morphology and adhesion of GB cells, also evaluating RhoA-ROCK signaling and Na+/K+-ATPase β2 (AMOG) involvement.MethodsHuman (NG97) GB cells were treated with twelve subfractions (SFs—obtained by HPLC from PnV). Migration and invasion were evaluated by scratch wound healing and transwell assays, respectively. Cell morphology and actin cytoskeleton were shown by GFAP and phalloidin labeling. The assay with fibronectin coated well plate was made to evaluate cell adhesion. Western blotting demonstrated ROCK and AMOG levels and a ROCK inhibitor was used to verify the involvement of this pathway. Values were analyzed by the GraphPad Prism software package and the level of significance was determinate using one-way analysis of variance (ANOVA) followed by Dunnett’s multiple comparisons test.ResultsTwo (SF1 and SF11) of twelve SFs, decreased migration and invasion compared to untreated control cells. Both SFs also altered actin cytoskeleton, changed cell morphology and reduced adhesion. SF1 and SF11 increased ROCK expression and the inhibition of this protein abolished the effects of both subfractions on migration, morphology and adhesion (but not on invasion). SF11 also increased Na+/K+-ATPase β2.ConclusionAll components of the venom were evaluated and two SFs were able to impair human glioblastoma cells. The RhoA effector, ROCK, was shown to be involved in the mechanisms of both PnV components. It is possible that AMOG mediates the effect of SF11 on the invasion. Further investigations to isolate and biochemically characterize the molecules are underway.
Highlights
Glioblastoma (GB) cells have the ability to migrate and infiltrate the normal parenchyma, leading to the formation of recurrent tumors often adjacent to the surgical extraction site
Barreto et al Cancer Cell Int (2020) 20:576 that adhesion molecule on glia (AMOG) mediates the effect of SF11 on the invasion
GB accounts for 80% of primary neoplasms of the brain and is one of the deadliest solid tumors of the central nervous system (CNS), leading to 225,000 deaths worldwide each year [4, 5]
Summary
Glioblastoma (GB) cells have the ability to migrate and infiltrate the normal parenchyma, leading to the formation of recurrent tumors often adjacent to the surgical extraction site. Standard treatment usually includes surgery and chemotherapy with temozolomide [6]; studies have shown that at least 50% of patients do not respond to this chemotherapy, and even those who respond have low survival [7]. In the 1970s, the standard treatment protocol involved surgical removal of the tumor and radiotherapy, responsible for an average survival of 9 months. A multi-target therapy is necessary, making it more difficult to have a responsive medication Another potential cause of treatment failure is that GB consists of cells with a high capacity to infiltrate healthy tissue, making complete removal difficult by surgery [5]. Finding target-oriented molecular entities to regulate migration and invasion, preventing the infiltration and metastasis, has been a challenge in the antineoplastic pharmacology
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
