6-Gingerol Induced Apoptosis and Cell Cycle Arrest in Glioma Cells via MnSOD and ERK Phosphorylation Modulation
Sher-Wei Lim1,2, Wei-Chung Chen3, Huey-Jiun Ko4,5,6
1Department of Neurosurgery, Chi-Mei Medical Center, Tainan 702, Taiwan.
Abstract:
6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.
Insights
6-gingerol, a ginger compound, effectively targets glioblastoma by crossing the blood-brain barrier. It induces cancer cell death through energy disruption and cell cycle arrest, showing therapeutic potential.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options.
- 6-gingerol, a bioactive compound in ginger, exhibits anticancer effects.
- Understanding 6-gingerol's specific mechanisms in GBM is crucial for therapeutic development.
Purpose of the Study:
- To investigate the anti-cancer mechanisms of 6-gingerol against glioblastoma multiforme (GBM).
- To assess 6-gingerol's efficacy in crossing the blood-brain barrier compared to curcumin.
- To elucidate the molecular pathways targeted by 6-gingerol in GBM cells.
Main Methods:
- Assessing 6-gingerol's blood-brain barrier penetration.
- Evaluating 6-gingerol's effects on GBM cell proliferation and apoptosis.
- Analyzing changes in mitochondrial function, including reactive oxygen species (ROS) and membrane potential.
- Investigating the modulation of the EGFR-RAF-MEK-ERK signaling pathway and cell cycle progression.
Main Results:
- 6-gingerol demonstrated superior blood-brain barrier penetration compared to curcumin.
- 6-gingerol inhibited GBM cell proliferation and induced apoptosis.
- Treatment led to increased mitochondrial ROS (mtROS) and decreased mitochondrial membrane potential, linked to MnSOD downregulation.
- 6-gingerol caused G1 phase cell cycle arrest by inhibiting ERK phosphorylation via the EGFR-RAF pathway.
Conclusions:
- 6-gingerol effectively promotes GBM cell death by disrupting cellular energy homeostasis and arresting the cell cycle.
- Modulation of MnSOD and ROS levels, along with inhibition of the EGFR-RAF-MEK-ERK pathway, are key mechanisms.
- 6-gingerol shows significant potential as a therapeutic agent for glioblastoma, warranting further clinical investigation.
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