Gomisin J inhibits the glioma progression by inducing apoptosis and reducing HKII-regulated glycolysis.

Abstract

Glioma is a leading cause of central nervous system malignant tumor-associated deaths in the world. However, the molecular mechanisms for glioma progression are still unclear, lacking effective therapeutic strategies. Gomisin J (GomJ) is a derivative of lignan compound, and shows regulatory effects on virus, oxidative stress and tumor progression. However, the role of GomJ in the meditation of glioma progression has not been explored. In this study, we found that GomJ markedly reduced the proliferation of glioma cell lines. Mitochondrial apoptosis was highly induced by GomJ, as evidenced by the significantly up-regulated expression of cytoplastic Cyto-c and cleaved Caspase-3. In addition, mitochondrial membrane potential (MMP) and oxidative stress were highly triggered in GomJ-incubated glioma cells, accompanied with the glycolysis suppression. Importantly, we found that GomJ could dramatically reduce the expression of hexokinase II (HKII) in glioma cells. At the same time, the dissociation of HKII from voltage-dependent anion channel (VDAC) in mitochondria was markedly induced by GomJ, contributing to glycolytic repression. The in vivo experiments confirmed that GomJ obviously reduced the growth of glioma with HKII reduction and few side effects. Taken together, these results demonstrated that GomJ could inhibit the proliferation, induce apoptosis and restrain HKII-regulated glycolysis during glioma progression. Herein, GomJ with few toxicity might be served as a potential therapeutic strategy for the treatment of glioma in humans.

• Authors: Ruilong Li, Weidong Yang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 529 Issue 1 Pg. 15-22 (08 13 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 32560813 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier Inc.

Chemical References

• Antineoplastic Agents, Phytogenic
• Lignans
• Polycyclic Compounds
• Voltage-Dependent Anion Channels
• HK2 protein, human
• Hexokinase
• gomisin J

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Disease Progression
• Glioma (drug therapy, metabolism, pathology)
• Glycolysis (drug effects)
• Hexokinase (metabolism)
• Humans
• Lignans (pharmacology)
• Membrane Potential, Mitochondrial (drug effects)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Mitochondria (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Polycyclic Compounds (pharmacology)
• Schisandra (chemistry)
• Voltage-Dependent Anion Channels (metabolism)
• Xenograft Model Antitumor Assays