Abstract
There is a need for a comprehensive anti-cancer strategy that simultaneously targets abnormal proliferation, angiogenesis rates, and development of chemotherapy resistance. We have identified a small molecule, OT-404, that effectively inhibited proliferation and angiogenesis of either chemo-sensitive or -resistant human cancer cells and enhanced cancer cell sensitivity to different chemotherapy. In vivo studies of human tumor xenografts in nude mice showed that OT-404, used alone or encapsulated into nanoparticles, inhibited the growth of doxorubicin-resistant breast cancer MCF-7 by more than 80%, and by 95% when combined with doxorubicin. These findings provide evidence for the potential of OT-404 in cancer management.
Copyright © 2013. Published by Elsevier Ireland Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / administration & dosage
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Breast Neoplasms / blood supply
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Cell Proliferation / drug effects*
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Chemistry, Pharmaceutical
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Dose-Response Relationship, Drug
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Doxorubicin / administration & dosage
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Drug Resistance, Neoplasm / drug effects*
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Female
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Humans
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MCF-7 Cells
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Nude
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Nanocapsules
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Neovascularization, Physiologic / drug effects*
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Time Factors
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Tumor Burden / drug effects
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U937 Cells
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Xenograft Model Antitumor Assays
Substances
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Angiogenesis Inhibitors
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Nanocapsules
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Doxorubicin