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

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https://ir.library.oregonstate.edu/concern/articles/0k225d03t

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  • 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.
  • 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.
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  • 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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  • This work was supported by the National Institutes of Health (P01CA090890). Oregon State University mass spectrometry facility is supported in part by a grant from the National Institute of Environmental Health Science (P30ES000210).
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