Abstract
Background:
Apoptosis is an essential form of cell death, the failure of which can lead to cancer development. Cancer including leukemia is usually treated with chemotherapeutic drugs that can be effective, but frequently problems are encountered that impair the success of the treatment. Butyrate is a short-chain fatty acid that can have many effects on different cells, including apoptosis.
Methods:
The effect of a combination treatment with butyrate and antineoplastic agents Ara-C, etoposide and vincristine is evaluate on the leukemic cell line THP-1.
Results:
We show that butyrate increased apoptosis induced by the three agents as seen by measurement of DNA content, annexin exposure and morphological characteristics. We also demonstrate that the process of apoptosis induced by butyrate and chemotherapeutic drugs involves the participation of caspases and induced activation of caspase-3, -8 and -9.
Conclusions:
We believe that butyrate could be a promising therapeutic agent for the treatment of leukemia in combination with other antineoplastic drugs.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Chloromethyl Ketones / pharmacology
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Amino Acid Chloromethyl Ketones / therapeutic use
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Antineoplastic Agents / classification
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Apoptosis / drug effects
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Apoptosis / physiology
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Blotting, Western
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Butyrates / chemistry
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Butyrates / pharmacology*
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Butyrates / therapeutic use
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Caspase Inhibitors
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Caspases / metabolism
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Caspases / therapeutic use
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Cell Line, Tumor
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Cytarabine / pharmacology
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Cytarabine / therapeutic use
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DNA Replication / drug effects
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor / methods
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Drug Synergism*
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Drug Therapy, Combination
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Etoposide / pharmacology
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Etoposide / therapeutic use
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Humans
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Leukemia, Monocytic, Acute / drug therapy*
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Leukemia, Monocytic, Acute / metabolism
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Leukemia, Monocytic, Acute / pathology*
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Vincristine / pharmacology
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Vincristine / therapeutic use
Substances
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Amino Acid Chloromethyl Ketones
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Antineoplastic Agents
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Butyrates
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Caspase Inhibitors
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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Cytarabine
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Vincristine
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Etoposide
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Caspases