| 4-O-methylhonokiol, a peroxisome proliferator activated receptor gamma agonist, inhibits prostate tumor growth: p21 mediated suppression of NF-κB activity. | |
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MedLine Citation:
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PMID: 23043610 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: This study was performed to investigate the effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, on human prostate cancer cell growth and its mechanism of action. EXPERIMENTAL APPROACH: Anti-cancer effects of MH were examined using human prostate cancer or normal cells. The effects were validated by in vivo Xenograft animal model. KEY RESULTS: Pull-down assay and molecular docking study suggested that MH may directly bind to PPAR-γ and elevate its activity. In consistent with these results, MH increased transcriptional activity of PPAR-γ, while decreased NF-κB activity. Growth inhibition of human prostate cancer cells was achieved by MH, which was blunted by PPAR-γ antagonist (GW9662). MH caused apoptotic cell death and it was related to G(0) -G(1) phase cell cycle arrest. We found that MH increased expression of the cell cycle regulator p21, and apoptotic proteins, whereas the compound decreased phosphorylation of Rb and anti-apoptotic proteins. Small interfering RNA against p21 or transfection of p21 with mutation on cyclin D1/Cdk4 binding site blocked MH-induced cell growth inhibition, and inhibition of NF-κB activity. With animal studies, MH inhibited tumor growth, NF-κB activity and expression of anti-apoptotic proteins, whereas increased transcriptional activity and expression of PPAR-γ, and the expression of apoptotic proteins as well as p21 in tumor tissues. CONCLUSIONS AND IMPLICATION: These results indicate that MH may suppress growth of human prostate cancer cells through activation of PPAR-γ, suppression of NF-κB as well as arrest of cell cycle. Thus, MH might be a useful tool for treatment of prostate cancer. |
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Authors:
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N J Lee; J H Oh; J O Ban; J H Shim; H P Lee; J K Jung; B W Ahn; D Y Yoon; S B Han; Y W Ham; J T Hong |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-8 |
Journal Detail:
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Title: British journal of pharmacology Volume: - ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society. |
Affiliation:
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College of Pharmacy, Chungbuk National University, 48 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, South Korea; College of Medical Research Center, Chungbuk National University, 48 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, South Korea. |
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