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The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1.

Abstract

Resveratrol (Res), from the skin of red grapes, induces apoptosis in some malignant cells, but there are no reports on the apoptotic effect of Res on human malignant pleural mesothelioma. We found that Res interacts with specificity protein 1 (Sp1). The IC50 for Res was 17 µM in MSTO-211H cells. Cell viability was decreased and apoptotic cell death was increased by Res (0-60 µM). Res increased the Sub-G1 population in MSTO-211H cells and significantly suppressed Sp1 protein levels, but not Sp1 mRNA levels. Res modulated the expression of Sp1 regulatory proteins including p21, p27, cyclin D1, Mcl-1 and survivin in mesothelioma cells. After treatment with Res, apoptosis signaling cascades were activated by the activation of Bid, Bim, caspase-3 and PARP, upregulation of Bax and downregulation of Bcl-xL. Res (20 mg/kg daily for 4 weeks) effectively suppressed tumor growth in vivo in BALB/c athymic (nu+/nu+) mice injected with MSTO-211H cells, an effect that was mediated by inhibition of Sp1 expression and induction of apoptotic cell death. Our results strongly suggest that Sp1 is a novel molecular target of Res in human malignant pleural mesothelioma.

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  • Authors+Show Affiliations

    ,

    Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 330-090, Republic of Korea.

    , , , , , , ,

    Source

    MeSH

    Animals
    Apoptosis
    Apoptosis Regulatory Proteins
    BH3 Interacting Domain Death Agonist Protein
    Bcl-2-Like Protein 11
    Caspase 3
    Cell Line, Tumor
    Cyclin D1
    Cyclin-Dependent Kinase Inhibitor p21
    Cyclin-Dependent Kinase Inhibitor p27
    Humans
    Inhibitor of Apoptosis Proteins
    Membrane Proteins
    Mesothelioma
    Mice
    Mice, Inbred BALB C
    Mice, Nude
    Myeloid Cell Leukemia Sequence 1 Protein
    Pleural Neoplasms
    Poly(ADP-ribose) Polymerases
    Proto-Oncogene Proteins
    Proto-Oncogene Proteins c-bcl-2
    RNA, Messenger
    Resveratrol
    Sp1 Transcription Factor
    Stilbenes
    Survivin
    Transplantation, Heterologous
    bcl-2-Associated X Protein
    bcl-X Protein

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22552784

    Citation

    Lee, Kyung-Ae, et al. "The Flavonoid Resveratrol Suppresses Growth of Human Malignant Pleural Mesothelioma Cells Through Direct Inhibition of Specificity Protein 1." International Journal of Molecular Medicine, vol. 30, no. 1, 2012, pp. 21-7.
    Lee KA, Lee YJ, Ban JO, et al. The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1. Int J Mol Med. 2012;30(1):21-7.
    Lee, K. A., Lee, Y. J., Ban, J. O., Lee, Y. J., Lee, S. H., Cho, M. K., ... Shim, J. H. (2012). The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1. International Journal of Molecular Medicine, 30(1), pp. 21-7. doi:10.3892/ijmm.2012.978.
    Lee KA, et al. The Flavonoid Resveratrol Suppresses Growth of Human Malignant Pleural Mesothelioma Cells Through Direct Inhibition of Specificity Protein 1. Int J Mol Med. 2012;30(1):21-7. PubMed PMID: 22552784.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1. AU - Lee,Kyung-Ae, AU - Lee,Yong-Jin, AU - Ban,Jung Ok, AU - Lee,Yoon-Jin, AU - Lee,Sang-Han, AU - Cho,Moon-Kyun, AU - Nam,Hae-Seon, AU - Hong,Jin Tae, AU - Shim,Jung-Hyun, Y1 - 2012/04/23/ PY - 2012/02/01/received PY - 2012/04/02/accepted PY - 2012/5/4/entrez PY - 2012/5/4/pubmed PY - 2012/9/29/medline SP - 21 EP - 7 JF - International journal of molecular medicine JO - Int. J. Mol. Med. VL - 30 IS - 1 N2 - Resveratrol (Res), from the skin of red grapes, induces apoptosis in some malignant cells, but there are no reports on the apoptotic effect of Res on human malignant pleural mesothelioma. We found that Res interacts with specificity protein 1 (Sp1). The IC50 for Res was 17 µM in MSTO-211H cells. Cell viability was decreased and apoptotic cell death was increased by Res (0-60 µM). Res increased the Sub-G1 population in MSTO-211H cells and significantly suppressed Sp1 protein levels, but not Sp1 mRNA levels. Res modulated the expression of Sp1 regulatory proteins including p21, p27, cyclin D1, Mcl-1 and survivin in mesothelioma cells. After treatment with Res, apoptosis signaling cascades were activated by the activation of Bid, Bim, caspase-3 and PARP, upregulation of Bax and downregulation of Bcl-xL. Res (20 mg/kg daily for 4 weeks) effectively suppressed tumor growth in vivo in BALB/c athymic (nu+/nu+) mice injected with MSTO-211H cells, an effect that was mediated by inhibition of Sp1 expression and induction of apoptotic cell death. Our results strongly suggest that Sp1 is a novel molecular target of Res in human malignant pleural mesothelioma. SN - 1791-244X UR - https://www.unboundmedicine.com/medline/citation/22552784/full_citation/The_flavonoid_resveratrol_suppresses_growth_of_human_malignant_pleural_mesothelioma_cells_through_direct_inhibition_of_specificity_protein_1_ L2 - http://www.spandidos-publications.com/ijmm/30/1/21 DB - PRIME DP - Unbound Medicine ER -