Abstract
A series of novel anthraquinone-thiosemicarbazone derivatives in a tautomerizable keto-imine form was synthesized and tested for their in vitro cytotoxic activity against human cancer cells (HeLa, MDA-MB-361, MDA-MB-453, K562, A549) and human normal MRC-5 cells. Several compounds efficiently inhibited cancer cell growth at micromolar concentrations, especially against K562 and HeLa cells. As determined by flow cytometric analysis, anthraquinone-thiosemicarbazone caused significant increase in the number of sub-G1 phase of HeLa cells and apoptosis in a concentration-dependent manner. Also, inhibition of caspase-3, -8, and -9 with specific caspase inhibitors reduced the apoptosis mediated by the tested compounds in HeLa cells. All anthraquinone-thiosemicarbazones exhibit calf thymus DNA-binding activity, but no cleavage of plasmid DNA was observed.
Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anthraquinones / chemical synthesis
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Anthraquinones / chemistry
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Anthraquinones / pharmacology*
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Antioxidants / chemical synthesis
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Antioxidants / chemistry
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Antioxidants / pharmacology*
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Apoptosis / drug effects
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Binding Sites / drug effects
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Cattle
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Cell Cycle / drug effects
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Cell Proliferation / drug effects
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Cells, Cultured
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DNA / chemistry
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DNA / drug effects*
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Dose-Response Relationship, Drug
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Fibroblasts / cytology
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Fibroblasts / drug effects*
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HeLa Cells
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Humans
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K562 Cells
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Methane / analogs & derivatives
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Methane / chemistry*
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Molecular Structure
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Structure-Activity Relationship
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Thiosemicarbazones / chemical synthesis
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Thiosemicarbazones / chemistry
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Thiosemicarbazones / pharmacology*
Substances
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Anthraquinones
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Antineoplastic Agents
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Antioxidants
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Thiosemicarbazones
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DNA
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calf thymus DNA
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Methane