title: Glycoborinine induces apoptosis through mitochondrial pathway in HepG2 cells.
abstract: Glycoborinine (GB), a natural carbazole alkaloid isolated from Glycosmis pentaphylla, has been shown to be a potential molecule against cancer cells. In this study, the cell-signaling pathway of its anti-tumor activity was investigated. MTT assay result showed that GB inhibited HepG2 cell proliferation in a dose- and time-dependent manner and 50% inhibiting concentration (IC50) of GB-induced cell death was 39.7 μM for a period of 48 h. GB-induced HepG2 apoptosis was confirmed by Hochest 33258 staining and PI staining. The level of reactive oxygen species (ROS) was measured with H2DCF-DA staining and the change of mitochondrial membrane potential (△Ψ(m)) was analyzed with tetrechloro-tetraethylbenzimidazolcarbocyanine iodide (JC-1) probe. Results showed that GB at 12.5, 25, and 50 μM promoted ROS production. GB induced HepG2 apoptosis through a mitochondrial apoptotic pathway, which was demonstrated by GB-induced increase in the ratio of Bax/Bcl-2, cytochrome C release, the ratio of cleaved caspase-3/procaspase-3, and the ratio of cleaved poly ADP-ribose polymerase (cleaved PARP)/poly ADP-ribose polymerase (PARP). To summarize, this study demonstrated that GB could induce HepG2 apoptosis through the mitochondrial-dependent pathway, which might provide a promising approach to cure liver cancer with GB.
authors.affiliation: a Engineering Research Centre for the Protection and Utilization of Bioresource in Ethnic Area of Southern China, South-Central University for Nationalities , Wuhan 430074 , China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Shi-Ting
authors.initials: ST
authors.lastname: Tian
authors.forename: Rui-Yun
authors.initials: RY
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Mei
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Wang
authors.forename: Guang-Zhong
authors.initials: GZ
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology*; D002232:Carbocyanines; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D015394:Molecular Structure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D002227:Carbazoles; D002232:Carbocyanines; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C584906:glycoborinine; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3
keywords: anti-tumor activity; glycoborinine; mitochondrial apoptotic pathway