Abstract
We have previously demonstrated the pivotal role of Jnk-mediated Irf-3/c-Jun in regulating nuclear factor kappa-Β ligand (RANKL)-induced osteoclastogenesis. Here, we demonstrated that proanthocyanidins (PACs) target Irf-3 to alleviate breast cancer-induced activation of osteoclasts. We also found that PACs induced apoptosis of osteoclast precursors by upregulating the ratio of bax/bcl-2 and activating caspase-3 activity. Such bone protective effect also could be observed in a bone metastasis model of breast cancer. These findings provided a novel therapeutic intervention targeting abnormal bone metabolism to alleviate bone metastasis of breast cancer.
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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Bone Neoplasms / drug therapy*
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Bone Neoplasms / metabolism
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Bone Neoplasms / secondary*
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Breast Neoplasms / pathology*
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Cell Line, Tumor
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Culture Media, Conditioned / pharmacology
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Interferon Regulatory Factor-3 / genetics
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Interferon Regulatory Factor-3 / metabolism*
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Male
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Osteoclasts / drug effects
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Osteoclasts / metabolism
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Osteogenesis / drug effects
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Osteogenesis / physiology
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Proanthocyanidins / pharmacology*
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Proto-Oncogene Proteins c-jun / genetics
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Proto-Oncogene Proteins c-jun / metabolism*
Substances
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Culture Media, Conditioned
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Interferon Regulatory Factor-3
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Irf3 protein, mouse
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Proanthocyanidins
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Proto-Oncogene Proteins c-jun