https://scholars.lib.ntu.edu.tw/handle/123456789/365866
Title: | Ling Zhi-8 mediates p53-dependent growth arrest of lung cancer cells proliferation via the ribosomal protein S7-MDM2-p53 pathway | Authors: | Wu, C.-T. Lin, T.-Y. Hsu, H.-Y. FUU SHEU Ho, C.-M. Chen, E.I.T. |
Issue Date: | 2011 | Journal Volume: | 32 | Journal Issue: | 12 | Start page/Pages: | 1890-1896 | Source: | Carcinogenesis | Abstract: | Ling Zhi-8 (LZ-8), an immunomodulatory protein, is derived from and has been cloned from the medicinal mushroom Ganoderma lucidum (Reishi or Ling Zhi); this protein exhibits immunomodulating and antitumor properties. We investigated the effects of recombinant LZ-8 protein (rLZ-8) on the proliferation of A549 human lung cancer cells. Here, we showed that rLZ-8 inhibits cell growth and that this is correlated with increased G 1 arrest. The treatment of A549 cells with rLZ-8 activated p53 and p21 expression, and both the G 1 arrest and the antigrowth effect were found to be p53 dependent. It was further demonstrated that rLZ-8 inhibited tumor growth in mice transplanted with Lewis lung carcinoma cells. Interestingly, rLZ-8 treatment was found to lead to nucleolar stress (or ribosomal stress) as evidenced by inhibition of precursor ribosomal RNA synthesis and reduced polysome formation in A549 cells. These changes resulted in an increasing binding of ribosomal protein S7 to MDM2 and a decreased interaction between MDM2 and p53. Taking these results together, we have identified a novel rLZ-8 antitumor function that positively modulates p53 via ribosomal stress and inhibits lung cancer cell growth in vitro and in vivo. Our current results suggest that rLZ-8 may have potential as a therapeutic intervention for the treatment of cancers that contain wild-type p53 and high expression of MDM2. ? The Author 2011. Published by Oxford University Press. All rights reserved. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-81855206545&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/365866 |
DOI: | 10.1093/carcin/bgr221 | SDG/Keyword: | antineoplastic agent; immunomodulating agent; protein MDM2; protein p53; recombinant ling zhi 8; recombinant protein; ribosome protein; ribosome protein S7; ribosome RNA; unclassified drug; animal experiment; animal model; animal tissue; antineoplastic activity; article; cancer cell culture; cancer inhibition; cell cycle arrest; cell cycle G1 phase; cell cycle G2 phase; cell cycle S phase; cell proliferation; cell stress; cell viability; concentration response; controlled study; dose time effect relation; drug dose comparison; human; human cell; in vitro study; in vivo study; Lewis carcinoma; lung cancer; male; mouse; nonhuman; polysome; priority journal; protein expression; protein induction; protein protein interaction; RNA synthesis; Animals; Base Sequence; Cell Proliferation; DNA Primers; Fungal Proteins; Humans; Lung Neoplasms; Mice; Neoplasm Transplantation; Proto-Oncogene Proteins c-mdm2; Reverse Transcriptase Polymerase Chain Reaction; Ribosomal Proteins; RNA Interference; Tumor Cells, Cultured; Tumor Suppressor Protein p53 |
Appears in Collections: | 園藝暨景觀學系 |
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