Abstract
Isatis indigotica is a biennial herbaceous cruciferous medical herb with antipyretic, antiviral, anti-inflammatory, and anti-endotoxin activity. This study explored the chemotherapeutic potential of I indigotica on human hepatoma cells and investigated the mechanism by which metabolites from I indigotica inhibit hepatoma cell growth. Antitumor activity was discovered in dried I indigotica leaf chloroform extracts (CEDLI). In nude mice xenotransplanted with human hepatoma cells, CEDLI supplementation inhibited tumor growth by ~40% compared with nonsupplemented animals without affecting body weight/food intake. CEDLI induced sub-G1 cell cycle arrest and apoptosis in hepatoma cells. Furthermore, CEDLI activates p53 and Bax, reduces Bcl-2 expression, and causes mitochondrial stress and the release of apoptosis-inducing factor into the cytosol followed by its translocation into the nucleus, resulting in hepatoma cell apoptosis. This study provides novel in vivo evidence of I indigotica's antitumor activity. The chemotherapeutic activity against human hepatoma tumorigenesis was because of a distinguished caspase-independent apoptotic pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects*
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Apoptosis / physiology
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Apoptosis Inducing Factor / metabolism*
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Body Weight / 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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Caspase 3 / metabolism
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Caspase 9 / metabolism
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Caspase Inhibitors
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Caspases / metabolism*
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Cell Cycle / drug effects
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Cell Line, Transformed
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Cell Line, Tumor
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cell Survival / drug effects
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Drugs, Chinese Herbal / isolation & purification
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Drugs, Chinese Herbal / pharmacology
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Drugs, Chinese Herbal / therapeutic use*
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Eating / drug effects
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Female
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G1 Phase Cell Cycle Checkpoints / drug effects
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Humans
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Isatis / chemistry*
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JNK Mitogen-Activated Protein Kinases / metabolism
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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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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Organ Size / drug effects
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Phosphorylation / drug effects
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Tumor Suppressor Protein p53 / metabolism
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Xenograft Model Antitumor Assays
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bcl-2-Associated X Protein / metabolism
Substances
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AIFM1 protein, human
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Apoptosis Inducing Factor
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BAX protein, human
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Caspase Inhibitors
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Drugs, Chinese Herbal
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Proto-Oncogene Proteins c-bcl-2
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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JNK Mitogen-Activated Protein Kinases
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Caspase 3
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Caspase 9
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Caspases