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    National Tsing Hua University Institutional Repository > 生命科學院  > 生命科學系 > 期刊論文 >  Functional proteomic and structural insights into molecular targets related to the growth inhibitory effect of tanshinone IIA on HeLa cells


    Please use this identifier to cite or link to this item: http://nthur.lib.nthu.edu.tw/dspace/handle/987654321/48701


    Title: Functional proteomic and structural insights into molecular targets related to the growth inhibitory effect of tanshinone IIA on HeLa cells
    Authors: Pan TL;Hung YC;Wang PW;Chen ST;Hsu TK;Sintupisut N;Cheng CS;Lyu PC
    教師: 呂平江
    Date: 2010
    Publisher: Wiley-Blackwell
    Relation: PROTEOMICS,Wiley-Blackwell,Volume 10,Issue 5,4 Jan 2010,Pages 914 - 929
    Keywords: 2-DE
    Apoptosis
    Cell biology
    HeLa cell
    MALDI-TOF analysis
    MetaCoreTM
    Abstract: Certain antitumor agents have recently been extracted from the roots of Salvia miltiorrhiza Bunge. The diterpene derivative, tanshinone IIA, possesses cytotoxic activity against several human carcinoma cell lines. It also inhibits invasion and metastasis of cancer cells. In the present study, we isolated tanshinone IIA from S. miltiorrhiza, and it exhibited strong growth inhibition against human cervical cancer cells in dose- and time-dependent manners with a 50% cell growth inhibition value of 2.5 g/mL (8.49 M). Flow cytometric analysis of cell cycle progression revealed that G2/M arrest was initiated after a 24 h exposure to the drug. It also resulted in DNA fragmentation and degradation of poly (ADP-ribose) polymerase indicating that tanshinone IIA may be a potential antitumor agent. Furthermore, we performed a comprehensive proteomic analysis to survey global protein changes induced by tanshinone IIA treatment on HeLa cells. Significant changes in the levels of cytoskeleton proteins as well as stress-associated proteins were observed. Immunoblot analysis and immunofluorescence staining were used to confirm the levels of protein expression. Overexpression of the vimentin rescued these tanshinone IIA-induced events. Computational docking methods indicated that tanshinone IIA could stably bind to the -subunit of the microtubule protein. An interaction network analysis of these 12 proteins using MetaCoreTM software suggested that tanshinone IIA treatment regulated the expressions of proteins involved in apoptotic processes, spindle assembly, and p53 activation, including vimentin, Maspin, - and -tubulin, and GRP75. Taken together, our results suggest that tanshinone IIA strongly inhibited the growth of cervical cancer cells through interfering in the process of microtubule assembly, leading to G2/M phase arrest and sequent apoptosis. The success of this large-scale effort was assessed by a bioinformatics analysis of proteins through predictions of protein domains and possible functional roles. The possible contributions of these proteins to the cytotoxicity of tanshinone IIA provide potential opportunities for the development of cancer therapeutics.
    URI: http://eu.wiley.com/WileyCDA/Brand/id-35.html
    http://nthur.lib.nthu.edu.tw/dspace/handle/987654321/48701
    Appears in Collections:[生命科學系] 期刊論文

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