Abstract
Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole), one of the simplest naturally occurring alkaloids, was isolated from the leaves of the evergreen tree Ochrosia elliptica Labill (Apocynaceae). Here, we reported that ellipticine inhibited the cell growth of human hepatocellular carcinoma cell line HepG2 and provided molecular understanding of this effect. The XTT assay results showed that ellipticine decreased the cell viability of HepG2 cells in a dose- and time-dependent manner, and the IC50 value was 4.1 microM. Furthermore, apoptosis induction by ellipticine in HepG2 cells was verified by the appearance of DNA fragmentation and annexin V-FITC/propidium iodide (PI) staining assay. Ellipticine treatment was found to result in the upregulation of p53, Fas/APO-1 receptor and Fas ligand. Besides, ellipticine also initiated mitochondrial apoptotic pathway through regulation of Bcl-2 family proteins expression, alteration of mitochondrial membrane potential (DeltaPsim), and activation of caspase-9 and caspase-3. Taken together, ellipticine decreased the cell growth and induced apoptosis in HepG2 cell.
MeSH terms
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects*
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Carcinoma, Hepatocellular / drug therapy*
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / pathology
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Cell Line, Tumor
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Cell Proliferation
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DNA / drug effects
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DNA Fragmentation
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Ellipticines / pharmacology*
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Fas Ligand Protein
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Humans
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Liver Neoplasms / drug therapy*
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Mitochondria, Liver / drug effects
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Mitochondria, Liver / physiology
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Mitochondrial Membranes / drug effects
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Plant Extracts
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Tumor Necrosis Factors / genetics
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Tumor Necrosis Factors / metabolism
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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Up-Regulation / drug effects
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fas Receptor / genetics
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fas Receptor / metabolism
Substances
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Antineoplastic Agents
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Ellipticines
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FASLG protein, human
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Fas Ligand Protein
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Membrane Glycoproteins
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Plant Extracts
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Proto-Oncogene Proteins c-bcl-2
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Tumor Necrosis Factors
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Tumor Suppressor Protein p53
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fas Receptor
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ellipticine
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DNA