Harmine,a beta-carboline alkaloid,is widely distributed in the plants,marine creatures,insects, mammalians as well as in human tissues and body fluids.Harmine was originally isolated from seeds of Peganum harmal in 18...Harmine,a beta-carboline alkaloid,is widely distributed in the plants,marine creatures,insects, mammalians as well as in human tissues and body fluids.Harmine was originally isolated from seeds of Peganum harmal in 1847 having a core indole structure and a pyridine ring.Harmine has various types of pharmacological activities such as antimicrobial,antifungal,antitumor,cytotoxic, antiplasmodial,antioxidaant,antimutagenic,antigenotoxic and hallucinogenic properties.It acts on gamma-aminobutyric acid type A and monoamine oxidase A or B receptor,enhances insulin sensitivity and also produces vasorelaxant effect.Harmine prevents bone loss by suppressing osteoclastogenesis.The current review gives an overview on pharmacological activity and analytical techniques of harmine,which may be useful for researcheres to explore the hidden potential of harmine and and will also help in developing new drugs for the treatment of various diseases.展开更多
BACKGROUND:Harmine has antitumor and antinociceptive effects,and inhibits human DNA topoisomerase.However no detailed data are available on the mechanisms of action of harmine in hepatocellular carcinoma.This study ai...BACKGROUND:Harmine has antitumor and antinociceptive effects,and inhibits human DNA topoisomerase.However no detailed data are available on the mechanisms of action of harmine in hepatocellular carcinoma.This study aimed to investigate the effects of harmine on proliferation and apoptosis and the underlying mechanisms in the human hepatocellular carcinoma cell line HepG2.METHODS:The proliferation of HepG2 cells was determined by the cell counting kit-8 (CCK-8) assay and the clone formation test.The morphology of HepG2 cells was examined using fluorescence microscopy after Hoechst 33258 staining Annexin V/propidium iodide (PI) was used to analyze apoptosis and PI to analyze the cell cycle.Western blotting was used to assess expression of the apoptosis-regulated genes Bcl-2,Bax,Bcl-xl,Mcl-1,caspase-3,and caspase-9 Mitochondrial transmembrane potential (Ψ m) was determined using JC-1.RESULTS:Harmine inhibited the proliferation of HepG2 cells in a dose-dependent manner.Hoechst 33258 staining revealed nuclear fragmentation and chromosomal condensation,cell shrinkage,and attachment loss in HepG2 cells treated with harmine.The percentage of the sub/G1 fraction was increased in a concentration-dependent manner,indicating apoptotic cell death.PI staining showed that harmine changed the cell cycle distribution,by decreasing the proportion of cells inG0/G1 and increasing the proportion in S and G2/M.Harmine induced apoptosis in a concentration-dependent manner,with rates of 20.0%,32.7% and 64.9%,respectively.JC-1 revealed a decrease in Ψ m.Apoptosis of HepG2 cells was associated with caspase-3 and caspase-9 activation,down-regulation of Bcl-2,Mcl-1,and Bcl-xl,and no change in Bax.CONCLUSIONS:Harmine had an anti-proliferative effect in HepG2 cells by inducing apoptosis.Mitochondrial signal pathways were involved in the apoptosis.The cancer-specific selectivity shown in this study suggested that harmine is a promising novel drug for human hepatocellular carcinoma.展开更多
文摘Harmine,a beta-carboline alkaloid,is widely distributed in the plants,marine creatures,insects, mammalians as well as in human tissues and body fluids.Harmine was originally isolated from seeds of Peganum harmal in 1847 having a core indole structure and a pyridine ring.Harmine has various types of pharmacological activities such as antimicrobial,antifungal,antitumor,cytotoxic, antiplasmodial,antioxidaant,antimutagenic,antigenotoxic and hallucinogenic properties.It acts on gamma-aminobutyric acid type A and monoamine oxidase A or B receptor,enhances insulin sensitivity and also produces vasorelaxant effect.Harmine prevents bone loss by suppressing osteoclastogenesis.The current review gives an overview on pharmacological activity and analytical techniques of harmine,which may be useful for researcheres to explore the hidden potential of harmine and and will also help in developing new drugs for the treatment of various diseases.
基金supported by grants from the Sci-Tech Project Foundation of Guangdong Province,China (2010B031600248)the National Natural Science Foundation of China (30772131)
文摘BACKGROUND:Harmine has antitumor and antinociceptive effects,and inhibits human DNA topoisomerase.However no detailed data are available on the mechanisms of action of harmine in hepatocellular carcinoma.This study aimed to investigate the effects of harmine on proliferation and apoptosis and the underlying mechanisms in the human hepatocellular carcinoma cell line HepG2.METHODS:The proliferation of HepG2 cells was determined by the cell counting kit-8 (CCK-8) assay and the clone formation test.The morphology of HepG2 cells was examined using fluorescence microscopy after Hoechst 33258 staining Annexin V/propidium iodide (PI) was used to analyze apoptosis and PI to analyze the cell cycle.Western blotting was used to assess expression of the apoptosis-regulated genes Bcl-2,Bax,Bcl-xl,Mcl-1,caspase-3,and caspase-9 Mitochondrial transmembrane potential (Ψ m) was determined using JC-1.RESULTS:Harmine inhibited the proliferation of HepG2 cells in a dose-dependent manner.Hoechst 33258 staining revealed nuclear fragmentation and chromosomal condensation,cell shrinkage,and attachment loss in HepG2 cells treated with harmine.The percentage of the sub/G1 fraction was increased in a concentration-dependent manner,indicating apoptotic cell death.PI staining showed that harmine changed the cell cycle distribution,by decreasing the proportion of cells inG0/G1 and increasing the proportion in S and G2/M.Harmine induced apoptosis in a concentration-dependent manner,with rates of 20.0%,32.7% and 64.9%,respectively.JC-1 revealed a decrease in Ψ m.Apoptosis of HepG2 cells was associated with caspase-3 and caspase-9 activation,down-regulation of Bcl-2,Mcl-1,and Bcl-xl,and no change in Bax.CONCLUSIONS:Harmine had an anti-proliferative effect in HepG2 cells by inducing apoptosis.Mitochondrial signal pathways were involved in the apoptosis.The cancer-specific selectivity shown in this study suggested that harmine is a promising novel drug for human hepatocellular carcinoma.
