gingerol and Glioblastoma

Lycopene, gingerol, and silymarin have a potential anticancer activity in many types of neoplasms. Healthy lifestyle and proper diet are associated with a reduced risk of cancer and other diseases. Increasingly, clinical research focuses on the mechanisms of action of natural compounds and their impact on the development of cancer. The aim of the present study was to determine the effect of lycopene, gingerol, and silymarin on apoptosis, mitochondrial potential and caspase-3/7 activity in the U118-MG cell line.. Human glioblastoma cells were incubated with lycopene, [6]-gingerol, and silymarin for 24 and 48 h. Apoptosis was monitored using the Annexin V labelling, caspase-3/7 activity, and early hallmark of apoptosis were determined with mitochondrial membrane potential changes.. Our data showed a significant decrease in the viability glioblastoma cells U118-MG after 48 h treatment with lycopene, [6]-gingerol, and silymarin.. Our data could confirm the stimulative effects of used compounds on apoptosis and changes in mitochondrial potential in a dose-dependent manner.

Topics: Apoptosis; Biological Assay; Caspase 3; Caspase 7; Catechols; Cell Line, Tumor; Cell Survival; Drug Administration Schedule; Fatty Alcohols; Glioblastoma; Humans; Lycopene; Silymarin

Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Astrocytes; Caspase 3; Caspase 7; Catechols; Cell Line, Tumor; Fatty Alcohols; Glioblastoma; Humans; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Receptors, TNF-Related Apoptosis-Inducing Ligand; RNA, Small Interfering; TNF-Related Apoptosis-Inducing Ligand