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4-O-methylhonokiol, a PPAR? agonist, inhibits prostate tumour growth: p21-mediated suppression of NF-?B activity.

ABSTRACT: BACKGROUND AND PURPOSE: The effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, were investigated on human prostate cancer cells and its mechanism of action elucidated. EXPERIMENTAL APPROACH: The anti-cancer effects of MH were examined in prostate cancer and normal cells. The effects were validated in vivo using a mouse xenograft model. KEY RESULTS: MH increased the expression of PPAR? in prostate PC-3 and LNCap cells. The pull-down assay and molecular docking study indicated that MH directly binds to PPAR?. MH also increased transcriptional activity of PPAR? but decreased NF-?B activity. MH inhibited the growth of human prostate cancer cells, an effect attenuated by the PPAR? antagonist GW9662. MH induced apoptotic cell death and this was related to G(0) -G(1) phase cell cycle arrest. MH increased the expression of the cell cycle regulator p21, and apoptotic proteins, whereas it decreased phosphorylation of Rb and anti-apoptotic proteins. Transfection of PC3 cells with p21 siRNA or a p21 mutant plasmid on the cyclin D1/ cycline-dependent kinase 4 binding site abolished the effects of MH on cell growth, cell viability and related protein expression. In the animal studies, MH inhibited tumour growth, NF-?B activity and expression of anti-apoptotic proteins, whereas it increased the transcriptional activity and expression of PPAR?, and the expression of apoptotic proteins and p21 in tumour tissues. CONCLUSIONS AND IMPLICATION: MH inhibits growth of human prostate cancer cells through activation of PPAR?, suppression of NF-?B and arrest of the cell cycle. Thus, MH might be a useful tool for treatment of prostate cancer.

SUBMITTER: Lee NJ

PROVIDER: S-EPMC3594673 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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4-O-methylhonokiol, a PPARγ agonist, inhibits prostate tumour growth: p21-mediated suppression of NF-κB activity.

Lee N J NJ Oh J H JH Ban J O JO Shim J H JH Lee H P HP Jung J K JK Ahn B W BW Yoon D Y DY Han S B SB Ham Y W YW Hong J T JT

British journal of pharmacology 20130301 5

<h4>Background and purpose</h4>The effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, were investigated on human prostate cancer cells and its mechanism of action elucidated.<h4>Experimental approach</h4>The anti-cancer effects of MH were examined in prostate cancer and normal cells. The effects were validated in vivo using a mouse xenograft model.<h4>Key results</h4>MH increased the expression of PPARγ in prostate PC-3 and LNCap cells. The pull-down assay and molecular d ...[more]

PMID: 23043610

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Dataset Information

4-O-methylhonokiol, a PPAR? agonist, inhibits prostate tumour growth: p21-mediated suppression of NF-?B activity.

Publications

4-O-methylhonokiol, a PPARγ agonist, inhibits prostate tumour growth: p21-mediated suppression of NF-κB activity.

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