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Scoulerine affects microtubule structure, inhibits proliferation, arrests cell cycle and thus culminates in the apoptotic death of cancer cells

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216275%3A25310%2F18%3A39912784" target="_blank" >RIV/00216275:25310/18:39912784 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11150/18:10380087 RIV/00216208:11160/18:10380087

  • Result on the web

    <a href="https://www.nature.com/articles/s41598-018-22862-0#article-info" target="_blank" >https://www.nature.com/articles/s41598-018-22862-0#article-info</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1038/s41598-018-22862-0" target="_blank" >10.1038/s41598-018-22862-0</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Scoulerine affects microtubule structure, inhibits proliferation, arrests cell cycle and thus culminates in the apoptotic death of cancer cells

  • Original language description

    Scoulerine is an isoquinoline alkaloid, which indicated promising suppression of cancer cells growth. However, the mode of action (MOA) remained unclear. Cytotoxic and antiproliferative properties were determined in this study. Scoulerine reduces the mitochondrial dehydrogenases activity of the evaluated leukemic cells with IC50 values ranging from 2.7 to 6.5 mu M. The xCELLigence system revealed that scoulerine exerted potent antiproliferative activity in lung, ovarian and breast carcinoma cell lines. Jurkat and MOLT-4 leukemic cells treated with scoulerine were decreased in proliferation and viability. Scoulerine acted to inhibit proliferation through inducing G2 or M-phase cell cycle arrest, which correlates well with the observed breakdown of the microtubule network, increased Chk1 Ser345, Chk2 Thr68 and mitotic H3 Ser10 phosphorylation. Scoulerine was able to activate apoptosis, as determined by p53 upregulation, increase caspase activity, Annexin V and TUNEL labeling. Results highlight the potent antiproliferative and proapoptotic function of scoulerine in cancer cells caused by its ability to interfere with the microtubule elements of the cytoskeleton, checkpoint kinase signaling and p53 proteins. This is the first study of the mechanism of scoulerine at cellular and molecular level. Scoulerine is a potent antimitotic compound and that it merits further investigation as an anticancer drug.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2018

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Scientific Reports

  • ISSN

    2045-2322

  • e-ISSN

  • Volume of the periodical

    8

  • Issue of the periodical within the volume

    March

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    14

  • Pages from-to

    "4829-1"-"4829-14"

  • UT code for WoS article

    000427688100022

  • EID of the result in the Scopus database

    2-s2.0-85044197609