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Human glioblastoma is the most common and aggressive brain tumor. This disease involves several complex physiological processes that involve membrane adhesion receptors, notably integrins. Plants have been at the origin of many active molecules that have shown their effectiveness in the treatment of various cancers. In this work, we proposed to study the anticancer effects of a spontaneous plant: Ecballium elaterium. The interest was given to the anti-adhesive, anti-migratory, anti-proliferative and anti-angiogenic activities. The characterization of the extracts and compounds responsible for these activities was also carried out. The work showed for the first time that the seed oil of Ecballium elaterium and the cucurbitacin B purified from its leaves are endowed with an important anti-tumor activity. These substances act via vbeta3, 5beta1, and 6beta4 integrins in U87 cells and thus represent novel natural agents that target integrins in high-grade gliomas.