Sulforaphane Causes Cell Cycle Arrest and Apoptosis in Human Glioblastoma U87MG and U373MG Cell Lines under Hypoxic Conditions

Abstract

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumor. The median survival rate from diagnosis ranges from 15 to 17 months because the tumor is resistant to most therapeutic strategies. GBM exhibits microvascular hyperplasia and pronounced necrosis triggered by hypoxia. Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, has already demonstrated the ability to inhibit cell proliferation, by provoking cell cycle arrest, and leading to apoptosis in many cell lines. In this study, we investigated the antineoplastic effects of SFN [20–80 μM for 48 h] in GBM cells under normoxic and hypoxic conditions. Cell viability assays, flow cytometry, and Western blot results revealed that SFN could induce apoptosis of GBM cells in a dose-dependent manner, under both conditions. In particular, SFN significantly induced caspase 3/7 activation and DNA fragmentation. Moreover, our results demonstrated that SFN suppressed GBM cells proliferation by arresting the cell cycle at the S-phase, also under hypoxic condition, and that these effects may be due in part to its ability to induce oxidative stress by reducing glutathione levels and to increase the phosphorylation of extracellular signal-regulated kinases (ERKs). Overall, we hypothesized that SFN treatment might serve as a potential therapeutic strategy, alone or in combination, against GBM.

Potential mechanisms of cancer prevention and treatment by sulforaphane, a natural small molecule compound of plant-derived

“…SFN treatment increases the levels of cleaved Caspase-3 and Bax, decreases the levels of Bcl-2, generates ROS to induce apoptosis in glioblastoma cells, and exerts anticancer effects by inhibiting the activation of the STAT3 signaling pathway in cancer cells (Miao et al 2017 ). SFN significantly promotes apoptosis in glioblastoma cell lines through a mitochondria-dependent manner, manifested by cysteine asparaginase activation and DNA breaks (Sita et al 2021 ). Histone deacetylase (HDAC) is overexpressed in multiple cancer subtypes.…”