title: Embelin-induced brain glioma cell apoptosis and cell cycle arrest via the mitochondrial pathway.
abstract: Brain glioma is the most common malignant intracranial tumor and has become the focus of research on diseases of the central nervous system due to its high incidence and poor prognosis. As a small‑molecule inhibitor of X-linked inhibitor of apoptosis protein (XIAP), embelin has the ability to specifically inhibit XIAP to control and regulate the apoptosis of various types of tumor cells. However, to date, the mechanism of action for this effect is not well understood. The aim of this study was to investigate the role that the mitochondrial pathway plays in embelin-induced brain glioma cell apoptosis and the effect of embelin on the cell cycle. Brain glioma cells were treated with different doses of embelin. The MTT method was used to determine cell proliferation, and flow cytometry was used to determine apoptosis, as well as changes in the cell cycle and cell mitochondrial membrane potential. Western blot analysis was performed to determine the expression levels of apoptosis‑associated proteins, Bcl-2, Bcl-xL, Bax and Bak as well as cytochrome c. We found that embelin induced a time‑ and dose‑dependent apoptosis of brain glioma cells, and that it could arrest the cell cycle in the G0/G1 phase. Embelin also caused changes in brain glioma cell mitochondrial membrane potential. Additionally, embelin regulated the shifting of Bax and Bcl-2 to promote the mitochondrial release of cytochrome c, thus activating the caspase proteins to cause apoptosis. Thus, embelin induces apoptosis in brain glioma cells which is closely associated with the mitochondrial pathway.
authors.affiliation: Department of Internal Medicine-Neurology, Central Hospital of Nanyang, Nanyang 473009, PR China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Wang
authors.forename: Baochao
authors.initials: B
authors.lastname: Zhang
authors.forename: Jiandang
authors.initials: J
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D005910:Glioma; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D018797:Cell Cycle Proteins; D020169:Caspases; C010945:embelin