Abstract
Two new phenazine derivatives, aotaphenazine (1) and 5,10-dihydrophencomycin (2), were isolated from the ethyl acetate extract of Streptomyces sp. IFM 11694. In addition, the known 1-phenazinecarboxylic acid (3), phencomycin (4) and 1,6-phenazinedicarboxylic acid (5) were identified. The structures of the isolated compounds (1-5) were characterized by spectroscopic methods including NMR and mass spectrometry data. Compound 1 showed the ability to overcome tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance at concentration of 12.5 μM. Aotaphenazine (1) enhanced the levels of apoptosis inducing proteins DR4, DR5, p53 and also decreased the levels of cell survival protein Bcl-2 in TRAIL-resistant human gastric adenocarcinoma (AGS) cells in a dose-dependent manner.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / drug therapy*
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Adenocarcinoma / pathology
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / isolation & purification
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Cell Line, Tumor
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Dose-Response Relationship, Drug
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Drug Resistance, Neoplasm
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Humans
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Magnetic Resonance Spectroscopy / methods
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Mass Spectrometry / methods
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Phenazines / administration & dosage
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Phenazines / isolation & purification
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Phenazines / pharmacology*
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Stomach Neoplasms / drug therapy*
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Stomach Neoplasms / pathology
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Streptomyces / metabolism*
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TNF-Related Apoptosis-Inducing Ligand / metabolism*
Substances
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Antineoplastic Agents
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Phenazines
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Proto-Oncogene Proteins c-bcl-2
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TNF-Related Apoptosis-Inducing Ligand