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Cannabinoid WIN 55,212-2 Inhibits Human Glioma Cell Growth by Triggering ROS-Mediated Signal Pathways
Kun Wang1,2, Qian Wang1, Qinghao Li1
1Postdoctoral Workstation, Taian City Central Hospital, Tai'an, Shandong 271000, China.
Abstract:
Glioblastoma is a highly invasive primary malignant tumor of the central nervous system. Cannabinoid analogue WIN 55,212-2 (WIN) exhibited a novel anticancer effect against human tumors. However, the anticancer potential and underlying mechanism of WIN against human glioma remain unclear. Herein, the anticancer efficiency and mechanism of WIN in U251 human glioma cells were investigated. The results showed that WIN dose-dependently inhibited U251 cell proliferation, migration, and invasion in vitro. WIN treatment also effectively suppressed U251 tumor spheroids growth ex vivo. Further studies found that WIN induced significant apoptosis as convinced by the caspase-3 activation and release of cytochrome C. Mechanism investigation revealed that WIN triggered ROS-mediated DNA damage and caused dysfunction of VEGF-AKT/FAK signal axis. However, ROS inhibition effectively attenuated WIN-induced DNA damage and dysfunction of VEGF-AKT/FAK signal axis and eventually improved U251 cell proliferation, migration, and invasion. Taken together, our findings validated that WIN had the potential to inhibit U251 cell proliferation, migration, and invasion and induce apoptosis by triggering ROS-dependent DNA damage and dysfunction of VEGF-AKT/FAK signal axis.
Insights
The cannabinoid WIN 55,212-2 (WIN) inhibits glioblastoma cell growth, migration, and invasion. WIN induces apoptosis by triggering reactive oxygen species (ROS)-mediated DNA damage and disrupting the VEGF-AKT/FAK signaling pathway.
Area of Science:
- Neuro-oncology
- Molecular Pharmacology
- Cancer Biology
Background:
- Glioblastoma is a highly invasive central nervous system tumor.
- Cannabinoid analogue WIN 55,212-2 (WIN) shows anticancer effects.
- The mechanism of WIN against human glioma is not fully understood.
Purpose of the Study:
- Investigate the anticancer efficiency of WIN in U251 human glioma cells.
- Elucidate the underlying anticancer mechanism of WIN.
Main Methods:
- In vitro proliferation, migration, and invasion assays.
- Ex vivo tumor spheroid growth inhibition.
- Apoptosis assessment (caspase-3 activation, cytochrome C release).
- Reactive oxygen species (ROS) detection and inhibition.
- Analysis of VEGF-AKT/FAK signaling pathway.
Main Results:
- WIN dose-dependently inhibited U251 cell proliferation, migration, and invasion.
- WIN suppressed U251 tumor spheroid growth and induced apoptosis.
- WIN triggered ROS-mediated DNA damage and VEGF-AKT/FAK pathway dysfunction.
- ROS inhibition attenuated WIN's effects and restored cell proliferation, migration, and invasion.
Conclusions:
- WIN demonstrates significant anticancer potential against U251 human glioma cells.
- WIN's mechanism involves ROS-dependent DNA damage and VEGF-AKT/FAK pathway disruption.
- WIN warrants further investigation as a therapeutic agent for glioblastoma.
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