Abstract
Breast cancer cells express ABCG2 transporters, which mediate multidrug resistance. Discovering a novel compound that can suppress ABCG2 expression and restore drug sensitivity could be the key to improving breast cancer therapeutics. In the current work, one new nor-neolignan, asperjinone (1), as well as 12 other known compounds, was isolated from Aspergillus terreus. The structure of the new isolate was determined by spectroscopic methods. Among these isolates, terrein (2) displayed strong cytotoxicity against breast cancer MCF-7 cells. Treatment with terrein (2) significantly suppressed growth of ABCG2-expressing breast cancer cells. This suppressive effect was achieved by inducing apoptosis via activating the caspase-7 pathway and inhibiting the Akt signaling pathway, which led to a decrease in ABCG2-expressing cells and a reduction in the side-population phenotype.
© 2012 American Chemical Society and American Society of Pharmacognosy
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters / drug effects*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / isolation & purification*
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Antineoplastic Agents / pharmacology*
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Aspergillus / chemistry*
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Breast Neoplasms / metabolism
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Caspase 7 / genetics
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Caspase 7 / metabolism
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Cyclopentanes / chemistry
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Cyclopentanes / pharmacology*
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Drug Screening Assays, Antitumor
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Female
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Humans
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Lignans / chemistry
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Lignans / isolation & purification*
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Lignans / pharmacology*
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Molecular Structure
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Neoplasm Proteins / drug effects*
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Nuclear Magnetic Resonance, Biomolecular
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Proto-Oncogene Proteins c-akt / drug effects
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Taiwan
Substances
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ABCG2 protein, human
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters
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Antineoplastic Agents
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Cyclopentanes
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Lignans
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Neoplasm Proteins
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asperjinone
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terrein
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Proto-Oncogene Proteins c-akt
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Caspase 7