Embelin induces apoptosis in human glioma cells through inactivating NF-κB
Sang-Yoon Park1, Sung-Lyul Lim, Hyeung-Jin Jang
1Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
Abstract:
Aggressive tumor growth and diffuse tissue invasion are hallmarks of malignant glioma. Embelin is an active compound identified as a novel XIAP inhibitor from the Embelia ribes that exhibits various medicinal effects including anti-inflammatory and anti-cancer activities. In the present study, we investigated whether embelin could have a therapeutic effect in glioma. We found that embelin suppressed proliferation of human glioma cells, but not in normal immortalized human astrocytes. In addition, embelin induced apoptosis in human glioma cells by inhibiting NF-κB, which is a crucial transcription factor associated with several human diseases including cancer and controls multiple genes involved in tumor progression such as cell proliferation and survival. Intriguingly, embelin had no inhibitory effect on XIAP in glioma cells even though discovered as an XIAP inhibitor, but instead inhibited NF-κB activity by reducing nuclear translocation of p65 through decreasing phosphorylation and proteasomal degradation of IκBα in glioma cells. Furthermore, p65 overexpression decreased embelin-induced apoptosis in glioma cells. Taken together these results indicate that embelin could be a potent novel therapeutic modality for glioma via blocking cancer cell proliferation and inducing apoptosis by inhibiting NF-κB activity.
Insights
Embelin, a natural compound, effectively inhibits glioma cell proliferation and induces apoptosis by targeting NF-κB signaling. This study highlights embelin as a potential novel therapeutic for malignant glioma.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Malignant glioma is characterized by aggressive tumor growth and invasion.
- Embelin, derived from Embelia ribes, is known for anti-inflammatory and anti-cancer properties and acts as a novel XIAP inhibitor.
- The therapeutic potential of embelin in glioma remains to be fully elucidated.
Purpose of the Study:
- To investigate the therapeutic effect of embelin on human glioma cells.
- To determine the mechanism by which embelin exerts its anti-glioma effects.
Main Methods:
- Assessing embelin's effect on human glioma cell proliferation versus normal astrocytes.
- Investigating embelin's impact on apoptosis and NF-κB signaling pathway components (p65, IκBα).
- Evaluating the role of p65 in embelin-induced apoptosis.
Main Results:
- Embelin suppressed proliferation in human glioma cells but not in normal astrocytes.
- Embelin induced apoptosis in glioma cells by inhibiting NF-κB signaling.
- Embelin inhibited NF-κB activity by reducing p65 nuclear translocation via IκBα phosphorylation and degradation, independent of XIAP inhibition.
- Overexpression of p65 attenuated embelin-induced apoptosis.
Conclusions:
- Embelin demonstrates potent anti-glioma activity by inhibiting cell proliferation and inducing apoptosis.
- The therapeutic mechanism involves the inhibition of NF-κB signaling pathway.
- Embelin represents a promising novel therapeutic candidate for glioma treatment.
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