Arachidonoylethanolamide promotes cellular senescence in a human glioblastoma cell line

Glioblastomas are the most common and deadly primary brain tumors, with high mortality rates despite aggressive therapies. Cellular senescence is important for cancer development, as it limits tumor progression; however, it may also stimulate inflammation at the tumor microenvironment, promoting tumor development. Hence, modulation of senescence is an important target for cancer therapy. Endocannabinoids modulate energy metabolism and the functions of the immune and nervous systems and have shown significant anti-tumor effects in experimental conditions, inhibiting cell growth and proliferation, while promoting apoptosis. Altered endocannabinoid concentrations are related to development of different types of cancer, and recent studies have shown that endocannabinoids and their synthetic analogs are capable of modulating senescence in multiple tissues, affecting cell proliferation and survival. Nonetheless, their effects on cellular senescence in cancer have not been defined. This study explored the effect of the endocannabinoid arachidonoylethanolamide on the induction of cellular senescence in human glioblastoma cell line U-87MG. Our results show that direct supplementation of AEA decreases cell cycle progression, while increasing beta-galactosidase activity and expression of p21, in U-87MG cells, in a dose- and time-dependent manner. Our data suggest that arachidonoylethanolamide may be useful for the modulation of glioblastoma senescence and should be explored further as an adjuvant for cancer therapy.