Dihydroartemisinin inhibits prostate cancer via JARID2/miR-7/miR-34a-dependent downregulation of Axl View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-03

AUTHORS

Juliano D. Paccez, Kristal Duncan, Durairaj Sekar, Ricardo G. Correa, Yihong Wang, Xuesong Gu, Manoj Bashin, Kelly Chibale, Towia A. Libermann, Luiz F. Zerbini

ABSTRACT

Axl expression is deregulated in several cancer types, predicts poor overall patient survival and is linked to resistance to drug therapy. Here, we evaluated a library of natural compounds for inhibitors of Axl and identified dihydroartemisinin, the active principle of the anti-malarial drug artemisinin, as an Axl-inhibitor in prostate cancer. Dihydroartemisinin blocks Axl expression leading to apoptosis, decrease in cell proliferation, migration, and tumor development of prostate cancer cells. Dihydroartemisinin treatment synergizes with docetaxel, a standard of care in metastatic prostate cancer increasing overall survival of mice with human xenografts. Dihydroartemisinin control of miR-34a and miR-7 expression leads to inhibition of Axl expression in a process at least partially dependent on regulation of chromatin via methylation of histone H3 lysine 27 residues by Jumonji, AT-rich interaction domain containing 2 (JARID2), and the enhancer of zeste homolog 2. Our discovery of a previously unidentified miR-34a/miR-7/JARID2 pathway controlling dihydroartemisinin effects on Axl expression and inhibition of cancer cell proliferation, migration, invasion, and tumor formation provides new molecular mechanistic insights into dihydroartemisinin anticancer effect on prostate cancer with potential therapeutic implications. More... »

PAGES

14

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41389-019-0122-6

    DOI

    http://dx.doi.org/10.1038/s41389-019-0122-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112228071

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30783079


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