Abstract
Here, we report that TW01001, a novel piperazinedione compound, could be a new mitotic inhibitor for the treatment of non-small cell lung cancer by the following observations in A549 cells: (1) induction of cells to accumulate at G2/M phase, which ultimately led to cell apoptotic death, (2) accumulation of p53 and inhibition of survival signalings, and (3) induction of p53-independent autophagy. Taken together, our data suggested that TW01001 induces autophagy-p53-signaling pathway to cause mitotic arrest and cell growth inhibition in A549 cells and provides the framework for further development as a novel therapeutic agent for lung cancer treatment.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
MeSH terms
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Autophagy / drug effects
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Benzoates / pharmacology*
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Cycle Checkpoints / drug effects
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Cell Division / drug effects
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Cell Line, Tumor
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Diketopiperazines / pharmacology*
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G2 Phase / drug effects
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Humans
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Mitosis / drug effects*
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Piperazines / administration & dosage
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Piperazines / pharmacology
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Piperazines / therapeutic use*
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Signal Transduction
Substances
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3-((6-((5-benzylidene-3,6-dioxopiperazin-2-ylidene)methyl)pyridin-3-yloxy)methyl)benzoic acid
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Benzoates
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Diketopiperazines
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Piperazines
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3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione