Abstract
Potentiation of anti-breast cancer activity of an imidazopyridine-based PI3Kα inhibitor, HS-104, was investigated in human breast cancer cells. HS-104 shows strong inhibitory activity against recombinant PI3Kα isoform and the PI3K signaling pathway, resulting in anti-proliferative activity in breast cancer cells. It also induced cell cycle arrest at the G(2)/M phase as well as apoptosis. Furthermore, oral administration of HS-104 significantly inhibited the growth of tumor in SkBr3 mouse xenograft models. Therefore, HS-104 could be considered as a potential candidate for the treatment of human breast cancer.
Crown Copyright © 2011. Published by Elsevier Ireland Ltd. 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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Apoptosis / drug effects
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Blotting, Western
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / enzymology
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Breast Neoplasms / pathology
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Cell Cycle Checkpoints / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Enzyme Inhibitors / pharmacology*
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Female
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Fluorescent Antibody Technique
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Humans
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Imidazoles / pharmacology*
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Immunoenzyme Techniques
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Phosphatidylinositol 3-Kinase / metabolism
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Phosphoinositide-3 Kinase Inhibitors*
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Pyridines / pharmacology*
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Signal Transduction / drug effects
Substances
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Enzyme Inhibitors
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HS-104
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Imidazoles
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Phosphoinositide-3 Kinase Inhibitors
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Pyridines
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Phosphatidylinositol 3-Kinase