Abstract
Over-expression of the Bcl-2 anti-apoptotic proteins is closely related to tumorigenesis and associated with drug resistance. Here we report that luteolin, a main substance found in Flos Chrysanthemi, directly binds to and shows inhibitory activity against the Bcl-2 protein. We studied the binding mode of luteolin and its derivatives with target proteins, their structure-activity relationship, and their effect on the human leukemia cell line HL-60. The results suggest that luteolin and its derivatives with a benzyl group introduced to the B ring, are new small molecule Bcl-2 protein inhibitors, and their anti-tumor activity is likely related to their effect on the Bcl-2 protein.
Keywords:
Anti-tumor; Apoptosis; Bcl-2 protein; Flos Chrysanthemi; Luteolin.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents, Phytogenic / chemistry
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Antineoplastic Agents, Phytogenic / isolation & purification
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Antineoplastic Agents, Phytogenic / pharmacology*
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Apoptosis / drug effects
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Chrysanthemum / chemistry*
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Flowers / chemistry*
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HL-60 Cells
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Humans
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Luteolin / chemistry
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Luteolin / isolation & purification
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Luteolin / pharmacology*
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Models, Molecular
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Molecular Structure
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / isolation & purification
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Small Molecule Libraries / pharmacology*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents, Phytogenic
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Proto-Oncogene Proteins c-bcl-2
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Small Molecule Libraries
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Luteolin