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 G0 -G1 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.
Written by:
Lee NJ, Oh JH, Ban JO, Shim JH, Lee HP, Jung JK, Ahn BW, Yoon DY, Han SB, Ham YW, Hong JT. Are you the author?
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.
Reference: Br J Pharmacol. 2012 Oct 8. Epub ahead of print.
doi: 10.1111/j.1476-5381.2012.02235.x
PubMed Abstract
PMID: 23043610
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