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SUV39H1/H3K9me3 attenuates sulforaphane-induced apoptotic signaling in PC3 prostate cancer cells

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Title SUV39H1/H3K9me3 attenuates sulforaphane-induced apoptotic signaling in PC3 prostate cancer cells
Names Watson, G. W. (creator)
Wickramasekara, S. (creator)
Palomera-Sanchez, Z. (creator)
Black, C. (creator)
Maier, C. S. (creator)
Williams, D. E. (creator)
Dashwood, R. H. (creator)
Ho, E. (creator)
Date Issued 2014-12-08 (iso8601)
Note This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by the Nature Publishing Group. The published article can be found at: http://www.nature.com/oncsis/index.html.
Abstract The isothiocyanate sulforaphane is a promising molecule for development as a therapeutic agent for patients with metastatic
prostate cancer. Sulforaphane induces apoptosis in advanced prostate cancer cells, slows disease progression in vivo and is well
tolerated at pharmacological doses. However, the underlying mechanism(s) responsible for cancer suppression remain to be fully
elucidated. In this investigation we demonstrate that sulforaphane induces posttranslational modification of histone
methyltransferase SUV39H1 in metastatic, androgen receptor-negative PC3 prostate cancer cells. Sulforaphane stimulates
ubiquitination and acetylation of SUV39H1 within a C-terminal nuclear localization signal peptide motif and coincides with its
dissociation from chromatin and a decrease in global trimethyl-histone H3 lysine 9 (H3K9me3) levels. Exogenous SUV39H1
expression leads to an increase in H3K9me3 and decreases sulforaphane-induced apoptotic signaling. SUV39H1 is thus identified as
a novel mediator of sulforaphane cytotoxicity in PC3 cells. Our results also suggest SUV39H1 dynamics as a new therapeutic target
in advanced prostate cancers.
Genre Article
Access Condition http://creativecommons.org/licenses/by-nc-nd/3.0/us/
Identifier Watson, G. W., Wickramasekara, S., Palomera-Sanchez, Z., Black, C., Maier, C. S., Williams, D. E., ... & Ho, E. (2014). SUV39H1/H3K9me3 attenuates sulforaphane-induced apoptotic signaling in PC3 prostate cancer cells. Oncogenesis, 3, e131. doi:10.1038/oncsis.2014.47

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