The novel marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol exhibits anticancer activity by regulating multiple signaling pathways in human glioblastoma cells: Blocking EGF signaling.

Glioblastoma is the most common adult malignant brain tumor. This tumor is aggressive and the most lethal. Trials to improve the outcome of patients with this tumor remain critical. There are no effective therapies for malignant glioma. Glioblastoma is characterized by ligand-independent overexpression of epidermal growth factor (EGF) receptors. EGF receptor signaling can promote tumorigenesis by increasing cell proliferation and tissue invasion and by inhibiting apoptosis of cancer cells. The marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) has been shown to block oxidative stress by scavenging free radicals in various cell types. This study investigates the effects of DHMBA on human glioblastoma cells in vitro. Glioblastoma cells were cultured in DMEM-low glucose containing 10% fetal bovine serum (FBS) in the presence of DHMBA (0.1-250 μM). Culturing with DHMBA significantly suppressed cell proliferation in the presence of FBS or EGF. Mechanistically, DHMBA treatment significantly decreased the levels of PI3-kinase 100α, Akt, MAPK, phosphor-MAPK, and mTOR, which are promoters of cell growth, and increased the levels of tumor suppressors p53, p21, and Rb, leading to the reduction of cancer cell growth. DHMBA treatment significantly stimulated the death of glioblastoma cells by increasing the levels of caspase-3 and cleaved caspase-3. In addition, culture with DHMBA significantly inhibited metastatic activity, including adhesion and migration of cancer cells. Thus, DHMBA may have inhibitory effects on the activity of human glioblastoma cells in vitro. This study may provide a new strategy for the treatment of glioblastoma tumors.